Affinage

MARK2

Serine/threonine-protein kinase MARK2 · UniProt Q7KZI7

Length
788 aa
Mass
87.9 kDa
Annotated
2026-06-10
87 papers in source corpus 44 papers cited in narrative 46 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MARK2 (Par-1b/EMK1) is a serine/threonine kinase that acts as a master regulator of cell polarity and cytoskeletal organization by phosphorylating microtubule-associated and cytoskeletal substrates to control their localization and activity (PMID:17360912, PMID:22072711). Its activity is set by a layered regulatory code: GSK-3β phosphorylates the activation loop (Ser-212) to switch the kinase on (PMID:16257959), aPKC phosphorylates Thr595 to drive 14-3-3/PAR-5 binding and dissociation from the lateral membrane (PMID:15324659), Dishevelled-dependent phosphorylation at Thr-324 governs membrane accumulation and microtubule output (PMID:18760999), reciprocal acetylation by CBP inhibits the kinase (PMID:35469920), and nucleic-acid-driven multimerization through the spacer region potentiates catalytic activity (PMID:35743080). A defining function is the detachment of microtubule-associated proteins: MARK2 phosphorylates tau at Ser-262 to remove it from microtubule tracks, reversing tau-induced transport block and rescuing neuronal organelle transport (PMID:17360912, PMID:16257959). It coordinates broader cytoskeletal architecture by phosphorylating GEF-H1 to inhibit RhoA-dependent stress fibers and release it from microtubules (PMID:22072711, PMID:21513698), myosin II regulatory light chain to promote contractility and focal-adhesion-based directional migration (PMID:35594862), and CAMSAP2 at Ser835 to control Golgi-anchored microtubules during migration (PMID:40333320). Through these activities MARK2 governs epithelial apical-basal and lumen polarity—phosphorylating Rab11-FIP2, Rab11-FIP1, RNF41, and IRSp53 to direct junction reassembly, receptor targeting, and lumen positioning (PMID:16775013, PMID:21282462, PMID:24259665, PMID:28396819)—as well as neuronal migration, axon specification, and polarized vesicle transport via kinesin motors KIF13B/GAKIN and KIF13A (PMID:18509032, PMID:20194617, PMID:38709923). MARK2 also directs mitotic spindle centering by tuning microtubule dynamics through MCAK (PMID:29941476). Beyond polarity, MARK2 phosphorylates eIF2α as a fifth eIF2α kinase in a PKCδ-driven proteotoxic stress response (PMID:33705388), regulates the circadian clock by stabilizing and phosphorylating PER2 at Ser662 (PMID:41812650), and drives oncogenic Hippo signaling by directly phosphorylating NF2 and YAP/TAZ to oppose LATS1/2 tumor suppression (PMID:31080060, PMID:39058094). The H. pylori oncoprotein CagA binds and inhibits MARK2 to disrupt epithelial polarity and generate genomic instability (PMID:18005242, PMID:19016760, PMID:30580666), a mechanism that has been repurposed as a catalytic MARK2/3 inhibitor that regresses tumors (PMID:39058094). Human MARK2 loss-of-function causes autism-spectrum neurodevelopmental deficits through downregulated WNT/β-catenin signaling (PMID:39419027).

Mechanistic history

Synthesis pass · year-by-year structured walk · 28 steps
  1. 2004 High

    Established how MARK2 membrane localization is controlled, defining aPKC as the upstream kinase that excludes Par-1b from the apical domain to establish epithelial polarity.

    Evidence T595A mutagenesis, 14-3-3 co-IP, and live imaging in polarized MDCK cells

    PMID:15324659

    Open questions at the time
    • Did not address how membrane-bound versus cytosolic MARK2 differ in substrate access
    • Phosphatase reversing T595 not identified
  2. 2005 High

    Placed MARK2 within an activating kinase cascade, showing GSK-3β phosphorylates the activation loop to switch on MARK2-mediated tau phosphorylation.

    Evidence In vitro kinase assay with recombinant GSK-3β/MARK2, siRNA epistasis, Ser-212 mutagenesis

    PMID:16257959

    Open questions at the time
    • Did not resolve whether GSK-3β acts on MARK2 in all polarity contexts
    • Relationship between Ser-212 and other activation-loop sites (Thr208) unmapped
  3. 2006 High

    Provided the structural basis for MARK2 autoregulation, revealing an unusual UBA-domain fold that docks onto the catalytic N-lobe.

    Evidence X-ray crystallography and SAXS of MARK1/MARK2 catalytic+UBA domains

    PMID:16803889

    Open questions at the time
    • Functional consequence of UBA docking on activity not directly tested
    • No full-length structure including KA1/spacer regions
  4. 2007 High

    Demonstrated the cell-biological payoff of tau phosphorylation, showing MARK2 detaches tau from microtubules to restore axonal transport and synaptic integrity.

    Evidence Tau + activated MARK2 transfection in hippocampal neurons with transport/spine/ATP readouts

    PMID:17360912

    Open questions at the time
    • Endogenous MARK2 contribution versus overexpression not separated
    • Did not address chronic tauopathy progression
  5. 2006 High

    Began defining the epithelial polarity substrate repertoire, identifying Rab11-FIP2 Ser227 as a MARK2 target controlling junction reassembly.

    Evidence In vitro kinase assay and S227A phosphomutant in MDCK calcium switch assay

    PMID:16775013

    Open questions at the time
    • Downstream vesicle trafficking step affected not defined
    • Endogenous phosphorylation kinetics not quantified
  6. 2007 Medium

    Linked MARK2 to a bacterial oncoprotein, showing H. pylori recruits MARK2 to the membrane via CagA to disrupt junctions and tubulogenesis.

    Evidence iTRAQ proteomics, co-IP, and 3D MDCK tubulogenesis assay

    PMID:18005242

    Open questions at the time
    • Single-study co-IP without reciprocal validation
    • Kinase-dependence of the junction defect not isolated here
  7. 2008 Medium

    Mapped the CagA-MARK2 inhibitory interface and tied binding strength to virulence, showing the CM sequence inhibits Par1b kinase activity.

    Evidence CM-variant binding and kinase assays with junction/hummingbird readouts

    PMID:19016760

    Open questions at the time
    • Structural detail of the CM-kinase contact not resolved
    • Did not address endogenous MARK2 thresholds in vivo
  8. 2008 High

    Established MARK2 in cortical development, showing kinase activity is required for radial neuronal migration via microtubule destabilization.

    Evidence In utero electroporation knockdown/overexpression with kinase-dead rescue and MT dynamics assays

    PMID:18509032

    Open questions at the time
    • Migration-relevant substrate(s) not identified in this system
    • Distinction from multipolar-bipolar transition incompletely defined
  9. 2008 Medium

    Showed that phosphorylation at Thr-324 controls MARK2 functional output by regulating its membrane partitioning rather than catalytic activity.

    Evidence T324E/T324A mutants with membrane localization, MT stabilization, and neurite assays

    PMID:18760999

    Open questions at the time
    • Kinase responsible for Thr-324 phosphorylation not identified
    • Single-lab phosphomimetic analysis
  10. 2009 High

    Expanded MARK2 polarity targets to motor proteins and basement-membrane signaling, phosphorylating utrophin Ser1258 to stabilize the utrophin-dystroglycan complex and RNF41 to direct laminin receptor localization.

    Evidence In vitro kinase assays, phosphosite mutagenesis (S1258A), and co-IP

    PMID:19945424

    Open questions at the time
    • Tissue context where utrophin phosphorylation matters not defined
    • RNF41 finding reported in a separate later study
  11. 2009 Medium

    Extended MARK2 polarity function to immune cells, showing TCR-induced phosphorylation and 14-3-3 binding relocalize Par1b and are required for MTOC polarization.

    Evidence TCR-stimulation phosphorylation, 14-3-3 co-IP, dominant-negative MTOC polarization assay

    PMID:19553522

    Open questions at the time
    • Phosphosite mediating relocalization not mapped
    • Dominant-negative may affect related paralogs
  12. 2010 High

    Connected MARK2 to neuronal axon specification by phosphorylating the kinesin GAKIN/KIF13B downstream of PI3K signaling.

    Evidence Co-IP, in vitro kinase assay, hippocampal neuron gain/loss-of-function, PI3K inhibition, siRNA epistasis

    PMID:20194617

    Open questions at the time
    • Precise phosphosites on KIF13B not fully enumerated
    • Link between PI3K and MARK2 activation step unresolved
  13. 2011 High

    Defined how MARK2 coordinates actin and microtubule systems, phosphorylating GEF-H1 to inhibit RhoA-GEF activity and release it from microtubules, and phosphorylating IRSp53 to control lumen polarity and ECM signaling.

    Evidence In vitro kinase assays, phosphosite mutagenesis, RhoA GEF activity assay, live imaging, IRSp53 rescue in MDCK

    PMID:21282462 PMID:21513698 PMID:22072711

    Open questions at the time
    • In vivo significance of GEF-H1 phosphorylation in migration untested here
    • Indirect S453/455 IRSp53 phosphorylation mechanism unidentified
  14. 2011 High

    Revealed a metabolic role, showing MARK2 phosphorylates KSR1 Ser392 to control ERK activation and peripheral insulin sensitivity.

    Evidence Co-IP, in vitro kinase assay, mark2−/− × KSR1 double-knockout mouse epistasis, glucose tolerance assays

    PMID:22206009

    Open questions at the time
    • Tissue-specific contribution of MARK2-KSR1 not dissected
    • Connection to canonical polarity functions unclear
  15. 2012 High

    Placed MARK2 at the actin-MT interface during directed migration as an effector downstream of Rac1 for leading-edge microtubule orientation, and linked it to mitochondrial transport by activating PINK1 at the PD-associated site Thr313.

    Evidence EB3-tracking RNAi screen with GFP rescue; in vitro PINK1 kinase assay with T313 mutagenesis and mitochondrial transport assays

    PMID:22238344 PMID:22848487

    Open questions at the time
    • MARK2 substrate at the leading edge not pinpointed in the Rac1 study
    • How MARK2 distinguishes anterograde versus retrograde PINK1 outputs unresolved
  16. 2012 Medium

    Connected MARK2 to TGFβ/BMP responsiveness through a Par1b/Dvl3/Smad4 complex that protects Smad4 from inhibitory ubiquitination.

    Evidence Co-IP, Xenopus mesoderm assay, TGFβ reporter, Smad4 ubiquitination assay

    PMID:22576663

    Open questions at the time
    • Whether MARK2 kinase activity is required not established
    • Single-lab complex characterization
  17. 2013 Medium

    Integrated MARK2 into asymmetric division and lumen positioning, showing it controls LGN-NuMA spindle orientation and lateral lumen polarity via ECM-regulated RhoA, and confirmed elevated MARK2-tau interactions in Alzheimer brain.

    Evidence Par1b gain/loss-of-function in MDCK/HepG2 with RhoA, LGN-NuMA, spindle readouts; proximity ligation assay in human AD tissue

    PMID:23001711 PMID:24165937 PMID:24358023

    Open questions at the time
    • PLA correlates association with disease but not causation
    • Mechanistic link between MARK2 membrane signaling and spindle machinery incomplete
  18. 2018 High

    Defined a direct mitotic role, showing MARK2 centers the spindle by tuning microtubule growth through the destabilizer MCAK.

    Evidence RNAi, quantitative live spindle imaging across hundreds of cells, MARK2+MCAK co-depletion epistasis

    PMID:29941476

    Open questions at the time
    • Direct MARK2 substrate controlling MCAK-dependent dynamics not identified
    • Connection to cortical signaling cues not resolved here
  19. 2019 High

    Identified MARK2 as an oncogenic Hippo regulator and a CagA-driven source of genomic instability, showing it disrupts the PAR1b-MST complex via CD44/HMW-HA and that CagA inhibition of Par1b generates DNA double-strand breaks.

    Evidence CD44-PAR1b and PAR1b-MST co-IP, Hippo reporters, tumor xenografts; CagA infection of primary gastric cells with γH2AX

    PMID:30580666 PMID:31080060

    Open questions at the time
    • Whether MST regulation requires MARK2 catalysis or scaffolding not separated
    • Mechanism linking Par1b inhibition to DSB formation undefined
  20. 2019 Medium

    Showed MARK2 integrates cortical actin status with spindle positioning by localizing to retraction fibres in a kinase-dependent manner.

    Evidence Kinase-dead localization studies, cytochalasin D perturbation, spindle off-centering assay

    PMID:31238822

    Open questions at the time
    • Retraction-fibre substrate unknown
    • Single-lab actin-perturbation analysis
  21. 2021 High

    Established MARK2 as a non-canonical eIF2α kinase and a transcriptional regulator, defining a PKCδ→MARK2→eIF2α proteotoxic stress cascade and a MARK2→Med17 axis linking polarity signaling to NF-κB-driven innate immunity.

    Evidence In vitro kinase assays, eIF2α phosphorylation in quadruple-kinase-KO cells, Med17 phosphomimetic mutants and transcriptome analysis

    PMID:33596087 PMID:33705388

    Open questions at the time
    • How MARK2 is partitioned between cytoskeletal and translational/transcriptional roles unclear
    • Med17 phosphorylation selectivity for inflammatory transcripts mechanistically undefined
  22. 2022 High

    Resolved how MARK2 directs migratory force and Golgi orientation, phosphorylating myosin II RLC for focal-adhesion-based motility, and connected it to chemoresistance via a CDK1→MARK2→HDAC4→YAP axis, plus a reciprocal CBP acetylation feedback loop controlling its activity.

    Evidence In vitro phosphorylation with isolated proteins, membrane-binding domain mutants, migration assays; Phos-tag screen, PDAC organoid/mouse models; in vitro CBP acetylation and kinase assays

    PMID:35469920 PMID:35594862 PMID:35780183

    Open questions at the time
    • Stoichiometry/sites of CBP acetylation on MARK2 not fully mapped
    • Crosstalk between mitotic CDK1 input and interphase MARK2 functions unresolved
  23. 2022 Medium

    Connected MARK2 activity to genome maintenance and revealed nucleic-acid-driven activation, showing it phosphorylates BRCA1 for nuclear translocation and that DNA/RNA binding to the spacer induces multimerization that potentiates kinase activity.

    Evidence In vitro multimerization/kinase assay, intracellular dsDNA introduction, BRCA1 localization, CagA inhibition

    PMID:35743080

    Open questions at the time
    • BRCA1 phosphosite not defined
    • Physiological trigger for nucleic-acid-driven multimerization unclear
  24. 2024 High

    Established MARK2/3 as the catalytic engine of oncogenic YAP/TAZ activity opposing LATS1/2, and demonstrated CagA-based catalytic inhibition as a tumor-regressing strategy; also defined MARK2 control of polarized kinesin cargo sorting via KIF13A.

    Evidence Paralog co-targeting CRISPR screens, in vitro phosphorylation of NF2/YAP/TAZ, CagA inhibitor with in vivo tumor regression; BioID, KIF13A/MARK2 knockouts, 14-3-3 co-IP with vesicle imaging

    PMID:38709923 PMID:39058094

    Open questions at the time
    • Relative contribution of MARK2 versus MARK3 to YAP/TAZ in each tumor type not parsed
    • Structural basis of CagA catalytic inhibition not resolved
  25. 2024 Medium

    Identified an activity-enhancing viral interaction, showing SARS-CoV-2 Orf9b engages the autoinhibitory KA1 domain to stimulate MARK2 kinase activity.

    Evidence Co-expression kinase assay, KA1 deletion mutant, T595 phosphorylation measurement

    PMID:38969617

    Open questions at the time
    • Downstream consequence of Orf9b-driven MARK2 activation in infection unknown
    • Single-lib HEK293 reconstitution
  26. 2024 Medium

    Linked MARK2 loss-of-function to human neurodevelopmental disease, showing it causes autism-spectrum deficits via WNT/β-catenin downregulation rescuable by lithium.

    Evidence Isogenic iPSC-derived neurons, RNA-seq, neural rosette/NPC assays, Mark2+/- mouse cortex, lithium rescue

    PMID:39419027

    Open questions at the time
    • Direct MARK2 substrate in WNT pathway not identified
    • Genotype-phenotype correlation in patients limited
  27. 2025 High

    Defined MARK2 as a clock kinase and a Golgi-organizing kinase, phosphorylating PER2 Ser662 to set circadian period and CAMSAP2 Ser835 to control Golgi reorientation during migration; also showed MARK2 drives pathogenic C9orf72 RAN translation via eIF2α.

    Evidence Biochemical purification + PER2 kinase assay with neuronal Mark2 KO mice; mass spectrometry phosphosite + CAMSAP2-USO1 co-IP + Golgi assay; RAN reporters and MARK2 KO in patient neurons/mice

    PMID:40333320 PMID:41231952 PMID:41812650

    Open questions at the time
    • How MARK2 toggles between clock, migration, and stress-translation outputs unresolved
    • Upstream activator of MARK2 in RAN-translation context not defined
  28. 2026 Medium

    Extended MARK2 into immune and oncogenic regulation, phosphorylating CRTC2 to restrain CD28/mTOR T-cell co-stimulation, GEF-H1 Ser645 to amplify TBK1/IFN-I antiviral signaling, dampening glial Toll/TLR inflammation, and stabilizing mutant p53 through its UBA/Spacer domains.

    Evidence T-cell conditional KO (preprint), CRTC2 phosphorylation; co-IP and GEF-H1 Ser645 phosphorylation with TBK1/IFN readouts; BV2 microglia and Drosophila Par-1 knockdown (preprint); mutp53 co-IP with domain-deletion mutants

    PMID:41678333 PMID:42019995

    Open questions at the time
    • Two of these findings are preprints awaiting peer review
    • Reconciliation of pro- versus anti-inflammatory roles across cell types unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How MARK2 selects among its dozens of substrates and switches between polarity, mitotic, stress-translation, circadian, immune, and oncogenic programs in a given cell remains unresolved.
  • No unifying model for context-dependent substrate selection
  • Quantitative contribution of each regulatory input (GSK-3β, aPKC, Dvl, CBP, multimerization, viral effectors) in vivo unknown
  • Structural basis of full-length autoregulation incompletely defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 19 GO:0016740 transferase activity 6 GO:0008092 cytoskeletal protein binding 3 GO:0098772 molecular function regulator activity 3 GO:0003723 RNA binding 1
Localization
GO:0005829 cytosol 3 GO:0005856 cytoskeleton 3 GO:0005886 plasma membrane 3 GO:0005815 microtubule organizing center 2 GO:0005634 nucleus 1
Pathway
R-HSA-1643685 Disease 5 R-HSA-162582 Signal Transduction 4 R-HSA-168256 Immune System 4 R-HSA-1266738 Developmental Biology 3 R-HSA-1640170 Cell Cycle 3 R-HSA-392499 Metabolism of proteins 2 R-HSA-8953897 Cellular responses to stimuli 2 R-HSA-9609507 Protein localization 2 R-HSA-9909396 Circadian clock 1
Partners
14-3-3CAGAGEF-H1KIF13AKIF13BMSTPER2PINK1

Evidence

Reading pass · 46 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2004 aPKC phosphorylates PAR-1b/MARK2 at threonine 595, which enhances binding with 14-3-3/PAR-5 and promotes dissociation of PAR-1b from the lateral membrane in polarized MDCK cells. T595A mutation causes PAR-1b leakage into the apical membrane, demonstrating that aPKC acts upstream of PAR-1b in epithelial polarity establishment and maintenance. Phosphorylation site mutagenesis (T595A), co-immunoprecipitation with 14-3-3, okadaic acid treatment, immunofluorescence in MDCK cells Current Biology High 15324659
2007 MARK2/Par-1 kinase activity removes tau from microtubule tracks, reversing tau-induced transport block in hippocampal neurons, and rescues dendritic spines, synapses, mitochondrial transport, and ATP levels. Transfection of tau and activated MARK2 in mature hippocampal neurons; spine/synapse markers, vesicle/organelle transport imaging, ATP measurement The Journal of Neuroscience High 17360912
2008 MARK2/Par-1 regulates radial neuronal migration in the developing cerebral cortex; reduced MARK2 stabilizes microtubules and stalls multipolar neurons at the intermediate zone border, while excess MARK2 causes loss of neuronal polarity. Kinase activity is specifically required for proper migration but not for multipolar-to-bipolar transition. In utero electroporation (knockdown and overexpression), microtubule dynamics assay in primary cultured neurons, kinase-dead MARK2 rescue experiments The Journal of Neuroscience High 18509032
2006 Crystal structure of the catalytic and ubiquitin-associated (UBA) domains of MARK2 revealed that the UBA domain has an unusual fold and binds to the N-terminal lobe of the catalytic domain. Comparison with MARK1 confirmed the same unusual UBA conformation and binding site across isoforms. X-ray crystallography of MARK1 and MARK2 catalytic+UBA domains; small angle X-ray scattering The Journal of Biological Chemistry High 16803889
2005 GSK-3β directly phosphorylates MARK2 on Ser-212 in the activation loop, activating MARK2 kinase activity. Activated MARK2 then phosphorylates tau at Ser-262. siRNA knockdown of either GSK-3β or MARK2 suppressed Ser-262 phosphorylation of tau, placing GSK-3β upstream of MARK2 in a tau phosphorylation cascade. In vitro kinase assay with recombinant GSK-3β and MARK2; siRNA knockdown; site-specific mutagenesis; tau phosphorylation readout The Journal of Biological Chemistry High 16257959
2006 MARK2 phosphorylates Rab11-FIP2 specifically on serine 227. Expression of a non-phosphorylatable Rab11-FIP2(S227A) mutant in MDCK cells causes a defect in the timely reestablishment of p120-containing junctional complexes after calcium switch, indicating this phosphorylation event regulates epithelial polarity establishment. In vitro kinase assay with recombinant MARK2; stable MDCK cell lines expressing WT or S227A Rab11-FIP2-EGFP; calcium switch polarity assay Molecular Biology of the Cell High 16775013
2007 H. pylori causes recruitment of MARK2 from cytosol to plasma membrane where it colocalizes with and interacts with the bacterial oncoprotein CagA. CagA-MARK2 association disrupts apical junctions and inhibits tubulogenesis in 3D MDCK culture models. iTRAQ proteomics of detergent-resistant membranes; co-immunoprecipitation (CagA-MARK2 interaction); 3D MDCK culture tubulogenesis assay Cellular Microbiology Medium 18005242
2008 The CagA multimerization (CM) sequence mediates CagA binding to PAR1b/MARK2 and inhibits PAR1b kinase activity. East Asian CagA CM sequences bind PAR1b more strongly than Western variants. The level of CagA-PAR1b binding activity correlates with the magnitude of junctional defects and hummingbird phenotype induction. Binding assays (CM sequence variants), kinase activity assays, tight junction disruption assays Cancer Science Medium 19016760
2009 PAR-1b interacts with the 8th and 9th spectrin-like repeats (R8-R9) of utrophin and phosphorylates Ser1258 within R9. Substitution of Ser1258 to alanine reduces the interaction between utrophin and dystroglycan, indicating that PAR-1b phosphorylation at this site stabilizes the utrophin-dystroglycan complex. PAR-1b also binds and phosphorylates the corresponding region of dystrophin. Co-immunoprecipitation; in vitro kinase assay with recombinant domains; site-directed mutagenesis (S1258A); colocalization by immunofluorescence Biochemical and Biophysical Research Communications High 19945424
2010 Par1b/MARK2 directly phosphorylates GAKIN/KIF13B, a kinesin superfamily motor protein, at conserved sites. In hippocampal neurons, overexpression of GAKIN/KIF13B induces extra axons, which is inhibited by Par1b in a kinase-activity-dependent manner. siRNA epistasis places GAKIN/KIF13B downstream of Par1b, and Par1b phosphorylation of GAKIN/KIF13B is downstream of PI3K signaling, linking Par1b to axon formation. Co-immunoprecipitation; in vitro kinase assay; gain/loss-of-function in hippocampal neurons; siRNA epistasis; PI3K pathway inhibition Molecular and Cellular Biology High 20194617
2011 PAR1b/MARK2 phosphorylates GEF-H1 on serine 885 and serine 959. This dual phosphorylation inhibits the RhoA-specific GEF activity of GEF-H1, preventing RhoA activation and RhoA-dependent stress fiber formation, thereby linking PAR1b to actin cytoskeletal regulation. In vitro kinase assay; site-directed mutagenesis (S885, S959); RhoA GEF activity assay; stress fiber staining The Journal of Biological Chemistry High 22072711
2011 Par1b/MARK2 phosphorylates GEF-H1 at three conserved serine residues, releasing GEF-H1 from microtubules, abrogating GEF-H1-induced microtubule stabilization and acetylation. A non-phosphorylatable GEF-H1 (3SA) mutant remained static on microtubules, while wild-type GEF-H1 showed dynamic movement, implicating MARK2 phosphorylation in regulating GEF-H1 localization dynamics. In vitro kinase assay; time-lapse live imaging of GFP-GEF-H1; microtubule acetylation assay; phosphomutant (3SA) characterization Biochemical and Biophysical Research Communications High 21513698
2011 Par1b/MARK2 phosphorylates IRSp53 on S366 directly and stimulates phosphorylation on S453/455 indirectly. A phosphorylation-deficient IRSp53 mutant rescues cell spreading and lumen polarity defects caused by Par1b overexpression, placing IRSp53 as a Par1b substrate linking Par1b to cell-ECM signaling and lumen polarity determination. In vitro kinase assay on cell lysates; site-directed mutagenesis; IRSp53 knockdown and rescue in MDCK cells; lumen polarity assay The Journal of Cell Biology High 21282462
2012 MARK2 phosphorylates and activates the cleaved form of PINK1 (ΔN-PINK1) at threonine 313 (T313), a site mutated to methionine in familial Parkinson disease. Mutation of T313 to Met or Glu in PINK1 causes abnormal mitochondrial distribution in neurons. MARK2 and PINK1 colocalize with mitochondria and regulate their transport, with MARK2 enhancing both ΔN-PINK1-promoted anterograde transport and full-length PINK1-promoted retrograde transport. In vitro kinase assay; site-directed mutagenesis (T313M, T313E); colocalization by immunofluorescence; mitochondrial transport assays in neurons The Journal of Biological Chemistry High 22238344
2012 MARK2 is required for leading edge microtubule (MT) growth and orientation downstream of Rac1 GTPase during directed cell migration. GFP-MARK2 localizes to lamellipodia in a Rac1-activity-dependent manner, and MARK2-depleted cells fail to polarize centrosomes or exhibit oriented MT growth, resulting in defective directional migration. RNAi screen with automated EB3 tracking; MARK2 siRNA knockdown; GFP-MARK2 rescue; wound-edge motility assay; centrosome polarization assay PLoS One High 22848487
2007 Par-1b/MARK2 promotes lateral lumen polarity in MDCK cells by inhibiting myosin II in a rho kinase-dependent manner. This process requires E-cadherin (even in an adhesion-defective state at the lateral domain), which serves as a targeting patch for lateral luminal surface establishment. Par1b overexpression in MDCK cells; myosin II inhibition; E-cadherin depletion/mutant rescue; 3D lumen polarity assay Molecular Biology of the Cell Medium 17409351
2009 Par1b is inducibly phosphorylated following TCR stimulation in T cells, which results in 14-3-3 protein binding and relocalization of Par1b from the membrane into the cytoplasm. A dominant-negative form of Par1b blocks TCR-induced MTOC polarization, indicating Par1b is required for T cell polarization. Phosphorylation detection after TCR stimulation; co-immunoprecipitation with 14-3-3; dominant-negative overexpression; MTOC polarization assay Journal of Immunology Medium 19553522
2013 MARK2 interacts with tau and phosphorylates tau at Ser-262 in NIH/3T3 cells. Staurosporine treatment reduces both MARK2-tau interaction and Ser-262 phosphorylation. Elevated MARK2-tau interactions are detected in post-mortem human Alzheimer's disease brain compared to non-demented controls. In situ proximity ligation assay (PLA); phospho-specific detection; staurosporine kinase inhibition; post-mortem human tissue analysis Journal of Alzheimer's Disease Medium 23001711
2013 Par-1b/MARK2 binds to and phosphorylates RNF41 (an E3 ubiquitin ligase) on serine 254. This phosphorylation is required for epithelial cells to localize laminin-111 receptors to their basolateral surfaces, anchor to laminin-111, and establish apical-basal polarity. Co-immunoprecipitation; in vitro kinase assay; site-directed mutagenesis (S254); laminin receptor localization assay; polarity assay in epithelial cells Journal of Cell Science High 24259665
2013 Par1b/MARK2 defines lumen position in concert with the position of the LGN-NuMA astral microtubule anchoring complex. Par1b signaling via ECM regulates RhoA/Rho-kinase activity at cell-cell contact sites; reduced RhoA activity (in Par1b-overexpressing MDCK cells or hepatic HepG2 cells) correlates with a single or no LGN-NuMA crescent, tilted spindles, and lateral lumen polarity. Par1b overexpression/depletion in MDCK and HepG2 cells; RhoA activity assay; LGN-NuMA localization imaging; spindle alignment measurements The Journal of Cell Biology Medium 24165937
2013 Par1b/MARK2 promotes LGN accumulation at the apicolateral subdomain of hepatocytes and capture of NuMA-positive astral microtubules, orienting the mitotic spindle to enable asymmetric segregation of apical plasma membrane domains to daughter cells during proliferating hepatocyte division. Par1b overexpression/knockdown; LGN and NuMA immunostaining; live imaging of dividing hepatocytes; apical domain segregation assay PLoS Biology Medium 24358023
2011 MARK2 phosphorylates KSR1 on Ser392, a critical regulator of KSR1 stability, subcellular location, and ERK activation. Disruption of KSR1 in mark2−/− mice reverses the increased insulin sensitivity from MARK2 deletion, placing MARK2 upstream of KSR1 in peripheral insulin signaling. Co-immunoprecipitation; in vitro kinase assay (MARK2 phosphorylates KSR1-Ser392); double knockout mouse genetic epistasis; glucose tolerance/insulin sensitivity assays PLoS One High 22206009
2019 High-molecular-weight hyaluronan (HMW-HA) activates Hippo signaling in breast epithelial cells by clustering CD44, which recruits PAR1b via the CD44 intracellular domain, disrupting the inhibitory PAR1b-MST complex. Once liberated from PAR1b, MST activates downstream Hippo signaling. Co-immunoprecipitation (CD44-PAR1b, PAR1b-MST complex); HMW-HA stimulation assays; Hippo pathway reporter assays; tumor xenograft model Developmental Cell High 31080060
2021 MARK2 directly phosphorylates eIF2α in response to proteotoxic stress. MARK2 activity is confirmed in cells lacking all four previously known eIF2α kinases. MARK2 itself is phosphorylated and activated by PKCδ, which senses protein misfolding through interaction with HSP90, defining a PKCδ→MARK2→eIF2α stress response cascade. In vitro kinase assay; eIF2α phosphorylation in cells lacking HRI/PKR/PERK/GCN2; MARK2 knockdown/knockout; PKCδ interaction with HSP90; ALS patient tissue analysis PLoS Biology High 33705388
2022 MARK2 directly phosphorylates myosin II regulatory light chain to promote myosin II contractility and stress fiber formation. MARK2 also indirectly promotes MYPT1 phosphorylation. Membrane association via the membrane-binding domain is required for MARK2 targeting to focal adhesions, where it promotes FAK phosphorylation and formation of migration-oriented focal adhesions for directional cell motility. In vitro phosphorylation assay with isolated proteins (MARK2 + myosin II RLC); MARK2 depletion with RNAi; membrane-binding domain deletion mutant; focal adhesion and stress fiber imaging; directional migration assay Current Biology High 35594862
2018 MARK2 maintains the mitotic spindle at the cell's geometric center; MARK2 depletion causes spindles to glide along the cell cortex, leading to failure in correct division plane selection. MARK2 modulates mitotic microtubule growth and length; co-depletion of MCAK (a microtubule destabilizer) rescues spindle off-centering, placing MARK2 function in regulation of mitotic microtubule dynamics for spindle centering. Protein depletion (RNAi); live-cell spindle imaging in 100s of cells; genetic epistasis (MARK2 + MCAK co-depletion); microtubule growth measurements The Journal of Cell Biology High 29941476
2019 MARK2 is present at actin-rich retraction fibres during mitosis in a kinase-activity-dependent manner (a kinase-dead mutant disrupts this specific localization). MARK2 at retraction fibres corrects mitotic spindle off-centring induced by actin disassembly, integrating cortical actin status with spindle positioning. Kinase-dead MARK2 mutant localization studies; actin perturbation (cytochalasin D); spindle off-centering assay; immunofluorescence and live imaging Open Biology Medium 31238822
2024 MARK2/MARK3 directly phosphorylate NF2 and YAP/TAZ, effectively reversing the tumor-suppressive activity of Hippo module kinases LATS1/2. MARK2/3 are absolute catalytic requirements for YAP/TAZ function in diverse carcinoma and sarcoma contexts, identified by paralog co-targeting CRISPR screens. CagA protein adapted as a catalytic inhibitor of MARK2/3 regresses established tumors in vivo. Paralog co-targeting CRISPR screens; in vitro phosphorylation of NF2 and YAP/TAZ by MARK2/3; CagA-based catalytic inhibitor; tumor regression in vivo Cancer Discovery High 39058094
2017 MARK2 phosphorylates Rab11-FIP1B/C at serine 234 in a consensus site. The spatial and temporal pattern of Rab11-FIP1 phosphorylation during calcium switch repolarization is distinct from Rab11-FIP2 phosphorylation. Non-phosphorylatable FIP1C(S234A) induces lateral lumen formation in MDCK cells, indicating this phosphorylation event modulates epithelial polarity. In vitro kinase assay (MARK2 + Rab11-FIP1); phospho-specific antibodies (pS234-FIP1, pS227-FIP2); MDCK calcium switch assay; GFP-FIP1C S234A overexpression Cellular Logistics Medium 28396819
2022 MARK2 is phosphorylated by CDK1 in response to antitubulin chemotherapeutics and during normal mitosis. MARK2 directly phosphorylates HDAC4, and phosphorylated HDAC4 promotes YAP activation and controls expression of YAP target genes induced by paclitaxel, revealing a MARK2-HDAC-YAP axis regulating paclitaxel chemosensitivity in pancreatic cancer cells. Phos-tag kinome-wide screen; in vitro MARK2 phosphorylation of HDAC4; CDK1 phosphorylation of MARK2; YAP reporter assay; PDAC organoid and mouse models Oncogene High 35780183
2008 Dishevelled (Dvl) promotes phosphorylation of Par1b at Thr-324 in a Dvl-dependent manner. A phospho-mimicking T324E mutation causes significant accumulation of Par1b at the membrane without affecting kinase activity. Membrane-accumulated Par1b (T324E) does not antagonize Dvl in microtubule stabilization or neurite extension, indicating that membrane localization regulated by Thr-324 phosphorylation determines Par1b's functional output on microtubule dynamics. Phosphorylation site identification (Thr-324); T324E phosphomimetic and T324A non-phosphorylatable mutants; membrane localization assay; microtubule stabilization assay; neurite extension assay Biochemical and Biophysical Research Communications Medium 18760999
2021 MARK2/Par1b activation enhances NF-κB-driven transcription of a specific subset of inflammatory transcripts by directly phosphorylating the core Mediator subunit Med17 at Ser152. Expression of S152D-Med17 (phosphomimetic) mimics MARK2 activation on downstream transcriptional regulation, while S152A-Med17 antagonizes it, establishing a MARK2-Med17 axis linking polarity signaling to innate immunity. In vitro phosphorylation of Med17 by recombinant MARK2; co-immunoprecipitation (MARK2-Med17 interaction); NF-κB transcriptional reporter; transcriptome analysis; phosphomimetic/non-phosphorylatable Med17 mutants Molecular Biology of the Cell High 33596087
2022 CBP acetyltransferase directly acetylates and inhibits MARK2 kinase activity. Conversely, MARK2 negatively regulates CBP, forming a reciprocal negative feedback loop between a kinase and an acetyltransferase, both of which modify tau in the context of Alzheimer's disease. In vitro acetylation assay (CBP acetylates MARK2); kinase activity assay; co-immunoprecipitation; tau phosphorylation/acetylation readouts The Journal of Biological Chemistry Medium 35469920
2024 MARK2 phosphorylates KIF13A at a 14-3-3 binding motif, strengthening KIF13A interaction with 14-3-3 and causing KIF13A to dissociate from transferrin receptor (TfR)-containing vesicles at the proximal axon. This prevents TfR vesicle entry into axons, ensuring their exclusive transport to dendrites. Knockout of MARK2 leads to axonal transport of TfR vesicles. Live-cell imaging; KIF13A knockout; BioID proximity labeling assay; MARK2 knockout; 14-3-3 co-immunoprecipitation Proceedings of the National Academy of Sciences of the United States of America High 38709923
2012 TGFβ/BMP signaling is regulated by a Par1b/Dvl3/Smad4 complex. Assembly of this complex, fostered by Wnt5a, prevents inhibitory ubiquitination of Smad4 by ectodermin/Trim33, thereby enabling TGFβ responsiveness. This was demonstrated in Xenopus mesoderm development and mammalian cells. Co-immunoprecipitation (Par1b/Dvl3/Smad4 complex); Xenopus mesoderm assay; TGFβ reporter assay in mammalian cells; Smad4 ubiquitination assay Cell Death and Differentiation Medium 22576663
2024 SARS-CoV-2 Orf9b enhances MARK2 kinase activity by interacting with the autoinhibitory KA1 domain of MARK2. Orf9b does not enhance the activity of a MARK2 mutant lacking the KA1 domain. Orf9b lowers inhibitory T595 phosphorylation of MARK2, though T595 is dispensable for Orf9b-mediated enhancement. Co-expression kinase activity assay in HEK293 cells; KA1 domain deletion mutant; T595 phosphorylation measurement; Orf9b-MARK2 interaction assay FEBS Letters Medium 38969617
2022 PAR1b/MARK2 mediates cytoplasmic-to-nuclear translocation of BRCA1 by phosphorylating it. Nucleic acids (both single- and double-stranded DNA/RNA) bind to the spacer region of PAR1b to induce multimerization, which markedly potentiates PAR1b kinase activity. CagA-mediated PAR1b inactivation reduces BRCA1 nuclear accumulation, leading to genomic instability. In vitro kinase assay with nucleic acid-mediated PAR1b multimerization; intracellular dsDNA introduction; BRCA1 nuclear localization assay; CagA-PAR1b interaction International Journal of Molecular Sciences Medium 35743080
2025 MARK2 is identified as a physiological kinase for PER2 at Ser662 through biochemical purification. MARK2 binds to and stabilizes PER2. Circadian period was shortened in Mark2-deficient cells in an S662-dependent manner, and neuronal-specific Mark2 knockout mice showed phase advancement and period shortening, establishing MARK2 as a regulator of the mammalian circadian clock. Biochemical purification (identified MARK2 as S662 kinase); in vitro kinase assay; Mark2-deficient cells (S662-dependent period shortening); neuronal-specific Mark2 knockout mice (circadian phenotype) Cell Chemical Biology High 41812650
2025 MARK2 phosphorylates CAMSAP2 at serine 835, which affects CAMSAP2's interaction with the Golgi-associated protein USO1 (but not CG-NAP or CLASPs), thereby regulating Golgi reorientation during directional cell migration by controlling microtubule anchoring to the Golgi. Mass spectrometry (phosphosite identification); in vitro/in-cell kinase assay; co-immunoprecipitation (CAMSAP2-USO1); Golgi reorientation assay; microtubule polarity distribution analysis eLife High 40333320
2025 MARK2 enhances RAN translation of C9orf72 GGGGCC-repeat-associated non-AUG (RAN) dipeptide repeat proteins by phosphorylating eIF2α under proteotoxic stress. Loss of MARK2 significantly suppresses RAN translation in reporter cells, patient-derived neurons, and a mouse model, and confers neuroprotection. MARK2-eIF2α signaling is upregulated in C9-ALS patient tissues. RAN translation reporter assay; MARK2 knockout in cells and mice; patient-derived neurons; C9-ALS patient tissue analysis; eIF2α phosphorylation assay Proceedings of the National Academy of Sciences of the United States of America High 41231952
2019 CagA-mediated inhibition of Par1b kinase promotes generation of DNA double-strand breaks (DSBs) in primary gastric epithelial cells, linking Par1b inhibition to genomic instability during H. pylori infection. CagA infection of primary human gastric epithelial cells (HGECs); DSB detection (γH2AX immunofluorescence); Par1b kinase inhibition by CagA CM domain Cell Cycle Medium 30580666
2024 MARK2 loss leads to downregulation of the WNT/β-catenin signaling pathway in neurons, contributing to neuronal developmental and functional deficits in autism spectrum disorder. iPSC-derived neurons from MARK2-loss-of-function individuals show anomalous polarity, disorganized neural rosettes, and imbalanced NPC proliferation/differentiation. Lithium treatment (activating WNT/β-catenin) rescues these deficits. CRISPR-engineered isogenic iPSCs; RNA-seq; neural rosette and NPC differentiation assays; Mark2+/- mouse cortical analysis; lithium treatment rescue American Journal of Human Genetics Medium 39419027
2026 MARK2 phosphorylates CRTC2 (CREB-regulated transcription coactivator 2), suppressing CREB-mediated transcription and mTOR activation in T cells. CD28 engagement lifts this MARK2-dependent inhibition, allowing CD28-driven proliferation, cytokine production, and glycolysis. MARK2 restrains the PI3K-AKT-mTORC1 pathway and acts as an intracellular checkpoint limiting CD28-mediated co-stimulation. T cell-specific conditional knockout mice; MARK2 phosphorylation of CRTC2; single-cell transcriptomics; PI3K-AKT-mTOR pathway readouts; proliferation and cytokine assays bioRxiv (preprint)preprint Medium
2026 MARK2 in glial cells negatively regulates Toll pathway-driven inflammatory signaling. MARK2 knockdown in BV2 microglia enhanced IL-6 expression in response to LPS and TLR7 agonist. In Drosophila, glial knockdown of Par-1 (MARK2 ortholog) enhanced Toll-mediated AMP expression and tau-induced neurodegeneration, while Par-1 overexpression suppressed them. MARK2 knockdown in BV2 microglia; cytokine (IL-6) measurement; PS19 tauopathy mouse brain (MARK2 expression in microglia states); Drosophila Par-1 glial knockdown/overexpression; AMP expression assay; photoreceptor neurodegeneration readout bioRxiv (preprint)preprint Medium
2026 MARK2 interacts with and stabilizes mutant p53 (mutp53) protein in TNBC cells through its UBA and Spacer domains. MARK2 is predominantly nuclear in TNBC cells. MARK2-ΔUBA or MARK2-ΔSpacer mutants fail to bind mutp53 and act as dominant-negative inhibitors suppressing TNBC progression. MARK2 does not alter wild-type p53 expression. Co-immunoprecipitation (MARK2-mutp53); domain deletion mutants (ΔUBA, ΔSpacer); siRNA knockdown of MARK2; mutp53 expression/stability assay; cell growth and migration assays Chinese Journal of Natural Medicines Medium 42019995
2026 MARK2 interacts with GEF-H1 and phosphorylates it at Ser645 in a microtubule-dependent manner. Phosphorylated GEF-H1 enhances TBK1 activation, promoting IFN-I and interferon-stimulated gene induction. MARK2 also transcriptionally upregulates GEF-H1 itself as an ISG, establishing a positive feedback loop that sustains antiviral innate immune signaling. Co-immunoprecipitation (MARK2-GEF-H1); in vitro/in-cell phosphorylation at Ser645; TBK1 activation assay; IFN-I reporter; ISG expression analysis Cell Reports Medium 41678333

Source papers

Stage 0 corpus · 87 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2004 aPKC acts upstream of PAR-1b in both the establishment and maintenance of mammalian epithelial polarity. Current biology : CB 251 15324659
2007 Missorting of tau in neurons causes degeneration of synapses that can be rescued by the kinase MARK2/Par-1. The Journal of neuroscience : the official journal of the Society for Neuroscience 237 17360912
2008 Accurate balance of the polarity kinase MARK2/Par-1 is required for proper cortical neuronal migration. The Journal of neuroscience : the official journal of the Society for Neuroscience 86 18509032
2019 High-Molecular-Weight Hyaluronan Is a Hippo Pathway Ligand Directing Cell Density-Dependent Growth Inhibition via PAR1b. Developmental cell 78 31080060
2007 Analysis of detergent-resistant membranes of Helicobacter pylori infected gastric adenocarcinoma cells reveals a role for MARK2/Par1b in CagA-mediated disruption of cellular polarity. Cellular microbiology 72 18005242
2007 Loss of the Par-1b/MARK2 polarity kinase leads to increased metabolic rate, decreased adiposity, and insulin hypersensitivity in vivo. Proceedings of the National Academy of Sciences of the United States of America 62 17372192
2010 Par1b/MARK2 phosphorylates kinesin-like motor protein GAKIN/KIF13B to regulate axon formation. Molecular and cellular biology 60 20194617
2012 Microtubule affinity-regulating kinase 2 (MARK2) turns on phosphatase and tensin homolog (PTEN)-induced kinase 1 (PINK1) at Thr-313, a mutation site in Parkinson disease: effects on mitochondrial transport. The Journal of biological chemistry 57 22238344
2011 Polarity-regulating kinase partitioning-defective 1b (PAR1b) phosphorylates guanine nucleotide exchange factor H1 (GEF-H1) to regulate RhoA-dependent actin cytoskeletal reorganization. The Journal of biological chemistry 53 22072711
2006 MARK2/EMK1/Par-1Balpha phosphorylation of Rab11-family interacting protein 2 is necessary for the timely establishment of polarity in Madin-Darby canine kidney cells. Molecular biology of the cell 52 16775013
2006 Structural variations in the catalytic and ubiquitin-associated domains of microtubule-associated protein/microtubule affinity regulating kinase (MARK) 1 and MARK2. The Journal of biological chemistry 52 16803889
2008 Structural and functional diversity in the PAR1b/MARK2-binding region of Helicobacter pylori CagA. Cancer science 51 19016760
2019 Genetic Overlap Between Alzheimer's Disease and Bipolar Disorder Implicates the MARK2 and VAC14 Genes. Frontiers in neuroscience 48 30930738
2005 GSK-3beta directly phosphorylates and activates MARK2/PAR-1. The Journal of biological chemistry 48 16257959
2013 Elevated MARK2-dependent phosphorylation of Tau in Alzheimer's disease. Journal of Alzheimer's disease : JAD 47 23001711
2006 PAR1b promotes cell-cell adhesion and inhibits dishevelled-mediated transformation of Madin-Darby canine kidney cells. Molecular biology of the cell 47 16707567
2011 The serine/threonine kinase Par1b regulates epithelial lumen polarity via IRSp53-mediated cell-ECM signaling. The Journal of cell biology 46 21282462
2016 Baicalin attenuates DDP (cisplatin) resistance in lung cancer by downregulating MARK2 and p-Akt. International journal of oncology 45 27878245
2009 The 8th and 9th tandem spectrin-like repeats of utrophin cooperatively form a functional unit to interact with polarity-regulating kinase PAR-1b. Biochemical and biophysical research communications 45 19945424
2008 Antagonistic effects of doublecortin and MARK2/Par-1 in the developing cerebral cortex. The Journal of neuroscience : the official journal of the Society for Neuroscience 44 19036994
2007 Par1b promotes hepatic-type lumen polarity in Madin Darby canine kidney cells via myosin II- and E-cadherin-dependent signaling. Molecular biology of the cell 43 17409351
2009 The polarity protein Par1b/EMK/MARK2 regulates T cell receptor-induced microtubule-organizing center polarization. Journal of immunology (Baltimore, Md. : 1950) 39 19553522
2011 Dynamic regulation of GEF-H1 localization at microtubules by Par1b/MARK2. Biochemical and biophysical research communications 35 21513698
2012 Automated screening of microtubule growth dynamics identifies MARK2 as a regulator of leading edge microtubules downstream of Rac1 in migrating cells. PloS one 34 22848487
2021 MARK2 phosphorylates eIF2α in response to proteotoxic stress. PLoS biology 33 33705388
2013 Par1b links lumen polarity with LGN-NuMA positioning for distinct epithelial cell division phenotypes. The Journal of cell biology 32 24165937
2006 Impairment of spatial learning and memory in ELKL Motif Kinase1 (EMK1/MARK2) knockout mice. Neurobiology of aging 32 17196307
1998 Human serine/threonine protein kinase EMK1: genomic structure and cDNA cloning of isoforms produced by alternative splicing. Cytogenetics and cell genetics 32 9730619
2022 MARK2 regulates directed cell migration through modulation of myosin II contractility and focal adhesion organization. Current biology : CB 29 35594862
2013 Par1b induces asymmetric inheritance of plasma membrane domains via LGN-dependent mitotic spindle orientation in proliferating hepatocytes. PLoS biology 29 24358023
2022 MARK2/4 promotes Warburg effect and cell growth in non-small cell lung carcinoma through the AMPKα1/mTOR/HIF-1α signaling pathway. Biochimica et biophysica acta. Molecular cell research 25 35192892
2003 Apical surface formation in MDCK cells: regulation by the serine/threonine kinase EMK1. Methods (San Diego, Calif.) 25 12798141
2018 In-Cell NMR Study of Tau and MARK2 Phosphorylated Tau. International journal of molecular sciences 23 30587819
2016 Impact of structural polymorphism for the Helicobacter pylori CagA oncoprotein on binding to polarity-regulating kinase PAR1b. Scientific reports 23 27445265
2013 Phosphorylation of the E3 ubiquitin ligase RNF41 by the kinase Par-1b is required for epithelial cell polarity. Journal of cell science 22 24259665
2022 MARK2 potentiate aerobic glycolysis-mediated cell growth in breast cancer through regulating mTOR/HIF-1α and p53 pathways. Journal of cellular biochemistry 21 35048405
2020 MARK2 enhances cisplatin resistance via PI3K/AKT/NF-κB signaling pathway in osteosarcoma cells. American journal of translational research 21 32509178
2024 MARK2/MARK3 Kinases Are Catalytic Codependencies of YAP/TAZ in Human Cancer. Cancer discovery 20 39058094
2011 MARK2/Par-1 guides the directionality of neuroblasts migrating to the olfactory bulb. Molecular and cellular neurosciences 20 22061967
2022 MARK2 regulates chemotherapeutic responses through class IIa HDAC-YAP axis in pancreatic cancer. Oncogene 19 35780183
2019 Loss of Par1b/MARK2 primes microglia during brain development and enhances their sensitivity to injury. Journal of neuroinflammation 19 30654821
2020 The inhibition of MARK2 suppresses cisplatin resistance of osteosarcoma stem cells by regulating DNA damage and repair. Journal of bone oncology 18 32368441
2016 Par-1b is required for morphogenesis and differentiation of myoepithelial cells during salivary gland development. Organogenesis 18 27841695
2019 Inhibition of polarity-regulating kinase PAR1b contributes to Helicobacter pylori inflicted DNA Double Strand Breaks in gastric cells. Cell cycle (Georgetown, Tex.) 16 30580666
2016 MARK2/Par1b Insufficiency Attenuates DVL Gene Transcription via Histone Deacetylation in Lumbosacral Spina Bifida. Molecular neurobiology 16 27714636
2018 Spindle rotation in human cells is reliant on a MARK2-mediated equatorial spindle-centering mechanism. The Journal of cell biology 15 29941476
2021 Long non-coding RNA ABHD11-AS1 facilitates the progression of cervical cancer by competitively binding to miR-330-5p and upregulating MARK2. Experimental cell research 14 34793775
2012 PAR1b takes the stage in the morphogenetic and motogenetic activity of Helicobacter pylori CagA oncoprotein. Cell adhesion & migration 14 23076215
2011 Regulation of glucose homeostasis by KSR1 and MARK2. PloS one 14 22206009
2022 MARK2 and MARK4 Regulate Sertoli Cell BTB Dynamics Through Microtubule and Actin Cytoskeletons. Endocrinology 13 35971301
2024 MARK2 variants cause autism spectrum disorder via the downregulation of WNT/β-catenin signaling pathway. American journal of human genetics 12 39419027
2017 Rab11-FIP1 phosphorylation by MARK2 regulates polarity in MDCK cells. Cellular logistics 12 28396819
2014 Emerging modes of PINK1 signaling: another task for MARK2. Frontiers in molecular neuroscience 12 24847206
2024 Role of MARK2 in the nervous system and cancer. Cancer gene therapy 11 38302729
1999 Expressed sequence tag (EST) phenotyping of HT-29 cells: cloning of ser/thr protein kinase EMK1, kinesin KIF3B, and of transcripts that include Alu repeated elements. Biochimica et biophysica acta 11 10395937
2019 MARK2/Par1b kinase present at centrosomes and retraction fibres corrects spindle off-centring induced by actin disassembly. Open biology 9 31238822
2012 Signaling crosstalk between TGFβ and Dishevelled/Par1b. Cell death and differentiation 9 22576663
2024 Cortactin-dependent control of Par1b-regulated epithelial cell polarity in Helicobacter infection. Cell insight 8 38646547
2017 MARK2 inhibits the growth of HeLa cells through AMPK and reverses epithelial-mesenchymal transition. Oncology reports 8 28560405
2017 Interconversion of inactive to active conformation of MARK2: Insights from molecular modeling and molecular dynamics simulation. Archives of biochemistry and biophysics 7 28711359
2004 Splicing alterations in human renal allografts: detection of a new splice variant of protein kinase Par1/Emk1 whose expression is associated with an increase of inflammation in protocol biopsies of transplanted patients. Biochimica et biophysica acta 7 15158914
2024 Neuronal connectivity, behavioral, and transcriptional alterations associated with the loss of MARK2. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 6 39436150
2023 Differential Chemoproteomics Reveals MARK2/3 as Cell Migration-Relevant Targets of the ALK Inhibitor Brigatinib. Chembiochem : a European journal of chemical biology 6 36922348
2008 Dishevelled-induced phosphorylation regulates membrane localization of Par1b. Biochemical and biophysical research communications 6 18760999
2022 A ZFP42/MARK2 regulatory network reduces the damage of retinal ganglion cells in glaucoma: a study based on GEO dataset and in vitro experiments. Apoptosis : an international journal on programmed cell death 5 36131186
2016 MARK2 Rescues Nogo-66-Induced Inhibition of Neurite Outgrowth via Regulating Microtubule-Associated Proteins in Neurons In Vitro. Neurochemical research 5 27465397
2022 Lanthanum Chloride Induces Axon Abnormality Through LKB1-MARK2 and LKB1-STK25-GM130 Signaling Pathways. Cellular and molecular neurobiology 4 35661286
2021 The cell polarity kinase Par1b/MARK2 activation selects specific NF-kB transcripts via phosphorylation of core mediator Med17/TRAP80. Molecular biology of the cell 4 33596087
2022 Identification of a reciprocal negative feedback loop between tau-modifying proteins MARK2 kinase and CBP acetyltransferase. The Journal of biological chemistry 3 35469920
2024 MicroRNA miR-7-5p targets MARK2 to control metamorphosis in Galeruca daurica. Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology 2 38521445
2014 Effects of T208E activating mutation on MARK2 protein structure and dynamics: Modeling and simulation. Molecular biology research communications 2 27843979
2024 MARK2 phosphorylates KIF13A at a 14-3-3 binding site to polarize vesicular transport of transferrin receptor within dendrites. Proceedings of the National Academy of Sciences of the United States of America 1 38709923
2024 SARS-CoV-2-derived protein Orf9b enhances MARK2 activity via interaction with the autoinhibitory KA1 domain. FEBS letters 1 38969617
2023 MARK2 phosphorylates KIF13A at a 14-3-3 binding site to polarize vesicular transport of transferrin receptor within dendrites. bioRxiv : the preprint server for biology 1 38105964
2023 Neuronal connectivity, behavioral, and transcriptional alterations associated with the loss of MARK2. bioRxiv : the preprint server for biology 1 38105965
2022 Kinase Activity of PAR1b, Which Mediates Nuclear Translocation of the BRCA1 Tumor Suppressor, Is Potentiated by Nucleic Acid-Mediated PAR1b Multimerization. International journal of molecular sciences 1 35743080
2026 MARK2 serves as a key regulator of host antiviral immunity through GEF-H1 phosphorylation. Cell reports 0 41678333
2026 Discovery of MARK2 as a physiological kinase for PER2 in the mammalian clock. Cell chemical biology 0 41812650
2026 Cryptic redundancy between PAR1b and PAR1a, two members of the PAR1 kinase family, in the survival of PAR1b-knockout mice. Scientific reports 0 41820498
2026 Loss-of-function variants in MARK2 cause neurodevelopmental disorder. HGG advances 0 41918168
2026 Targeting of MARK2, but not other MARKs, suppresses TNBC progression by inhibition of the mutant p53-driven signaling pathway. Chinese journal of natural medicines 0 42019995
2026 Case Report: Epileptic phenotype in a patient with a MARK2 variant: the first detailed description and review of the literature. Frontiers in pediatrics 0 42255910
2025 MARK2 regulates Golgi apparatus reorientation by phosphorylation of CAMSAP2 in directional cell migratio. eLife 0 40333320
2025 Identification of a de Novo MARK2 gene variant in a patient with autism spectrum disorder, epilepsy, and neurodevelopmental delay. Neurogenetics 0 40542891
2025 Bisphenol F promotes lung cancer progression by MARK2-driven stimulation of proliferation, suppression of ferroptosis, and activation of EMT. Ecotoxicology and environmental safety 0 41151288
2025 MARK2 regulates C9orf72 repeat-associated non-AUG translation. Proceedings of the National Academy of Sciences of the United States of America 0 41231952
2022 Validating MARK2 Gene Polymorphism as a Predictor of Response to Lithium Treatment in Bipolar Patients. Iranian biomedical journal 0 34953473

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