Affinage

Showing MAP4K1 — HPK1 is a alias.

MAP4K1

Mitogen-activated protein kinase kinase kinase kinase 1 · UniProt Q92918

Length
833 aa
Mass
91.3 kDa
Annotated
2026-06-10
100 papers in source corpus 32 papers cited in narrative 32 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MAP4K1/HPK1 is a hematopoietic Ste20-related serine/threonine kinase that operates as a signal-integrating hub linking immunoreceptor and stress inputs to the JNK/SAPK and NF-κB pathways, predominantly functioning as a negative regulator of lymphocyte and innate immune activation (PMID:8824585, PMID:9003777, PMID:10795738). It directly binds and phosphorylates MEKK1 and triggers JNK1 activation through parallel MEKK1→MKK4/SEK1 and TAK1→MKK4 and MLK3 routes, independently of Rac1/Cdc42 (PMID:8824585, PMID:9003777, PMID:9278437), and acts upstream of the IKK/NF-κB axis, in part by phosphorylating the CARMA1 linker at S549/S551/S552 to enable TCR-induced NF-κB activation (PMID:10523828, PMID:16341093, PMID:19706536). HPK1 is recruited into antigen-receptor signaling through proline-rich-motif interactions with the SH3 domains of Grb2, Gads/Grap2, Crk/CrkL, and the SLP-76-family adaptors SLP-76 and Clnk, and its catalytic activation upon TCR/BCR engagement depends on Src- and Syk/ZAP-70-family kinases and the LAT/SLP-76/BLNK adaptor network (PMID:9346925, PMID:9788432, PMID:10795738, PMID:11313918, PMID:11509653, PMID:15100220). Despite enabling NF-κB, HPK1 restrains the broader response: it suppresses TCR-induced AP-1/ERK signaling, phosphorylates BLNK at Thr152 to drive its 14-3-3 binding, ubiquitination, and degradation in B cells, and competes with ADAP for SLP-76 to dampen Rap1/LFA-1-mediated adhesion in T and B cells (PMID:10795738, PMID:20957749, PMID:22334673). A distinct PGE2/GPCR input activates HPK1 via PKA-dependent phosphorylation of activation-loop Ser171, bypassing the phosphotyrosine adaptor machinery (PMID:12522005, PMID:17895239). Caspase-3 cleavage at Asp385 splits HPK1 into a constitutively active N-terminal kinase fragment that drives JNK-dependent survival and monocytic differentiation, and a C-terminal fragment that sequesters the IKK complex to suppress NF-κB and sensitize lymphocytes to activation-induced cell death (PMID:10602493, PMID:11278403, PMID:16341093, PMID:17024227, PMID:17712048). Structurally, the kinase domain is trans-regulated through phosphorylation-state-dependent dimer remodeling, and the citron homology domain folds into a seven-bladed β-propellor that binds the kinase domain to inhibit activity, dock SLP-76, and stabilize the protein (PMID:31018963, PMID:38697971). In innate immunity HPK1 promotes DTX4-dependent K48-ubiquitination and proteasomal degradation of TBK1/IKKε to limit antiviral interferon responses, and loss or pharmacologic/PROTAC-mediated inhibition of HPK1 relieves T-cell and NK-cell dysfunction and enhances antitumor immunity (PMID:32860752, PMID:34908452, PMID:38828677).

Mechanistic history

Synthesis pass · year-by-year structured walk · 26 steps
  1. 1996 High

    Established HPK1 as a kinase that selectively channels signals into the JNK/SAPK pathway, defining its core catalytic output.

    Evidence Transfection epistasis with dominant-negative MEKK1/MKK4 and in vitro binding/phosphorylation in two independent studies

    PMID:8824585 PMID:9003777

    Open questions at the time
    • Did not identify physiological upstream activators
    • Selectivity for JNK over p38/ERK explained mechanistically only at pathway level
  2. 1997 High

    Mapped redundant MAP3K effectors (MLK3, TAK1) downstream of HPK1, showing the kinase feeds multiple parallel routes to JNK.

    Evidence Dominant-negative and constitutively active mutant epistasis in transfected cells

    PMID:9003777 PMID:9278437

    Open questions at the time
    • Direct phosphorylation of TAK1/MLK3 by HPK1 not demonstrated
    • Context determining which effector is used unknown
  3. 1997 High

    Identified adaptor-mediated recruitment of HPK1, explaining how it couples to tyrosine-kinase receptor signaling via Grb2 and to Crk/CrkL.

    Evidence In vitro SH3-domain binding, co-IP, and EGF stimulation assays

    PMID:9346925 PMID:9788432

    Open questions at the time
    • Functional consequence of Crk/CrkL phosphorylation not established
    • In vivo relevance of EGFR coupling unclear
  4. 1999 High

    Discovered caspase-3 cleavage at Asp385 as a switch that splits HPK1 into functionally distinct fragments, reframing it as an apoptosis-regulated kinase.

    Evidence In vitro caspase-3 cleavage, Asp385 mutagenesis, and adaptor co-IP

    PMID:10602493

    Open questions at the time
    • Physiological trigger of cleavage not defined at this stage
    • Fate of fragments in vivo unknown
  5. 1999 Medium

    Placed HPK1 upstream of the IKK/NF-κB pathway, extending its reach beyond JNK.

    Evidence Overexpression IKK kinase activity assays

    PMID:10523828

    Open questions at the time
    • No mutagenesis confirming direct IKK interaction
    • Whether activation is direct or via MEKK1 unresolved
  6. 2000 High

    Defined HPK1 as a TCR/BCR-activated negative regulator of the AP-1 pathway, establishing its central immunoregulatory role.

    Evidence Antigen-receptor stimulation with reciprocal gain/kinase-dead loss-of-function and adaptor requirements in T and B cells

    PMID:10795738

    Open questions at the time
    • Substrates mediating AP-1 suppression not yet identified
    • Distinction between positive NF-κB and negative AP-1 outputs unexplained
  7. 2001 High

    Resolved the activator-to-inhibitor switch: full-length kinase-active HPK1 activates NF-κB via IKKβ, while the C-terminal cleavage fragment is a dominant-negative NF-κB inhibitor.

    Evidence Truncation constructs, dominant-negative IKKβ, and NF-κB reporter assays in myeloid cells

    PMID:11278403

    Open questions at the time
    • Mechanism of IKK impairment by HPK1-C not yet structural
    • Endogenous IKK association not yet shown
  8. 2001 Medium

    Extended the adaptor map to Gads/Grap2 and Clnk, showing these SH3 partners enhance HPK1 activity and IL-2 transcription.

    Evidence In vitro binding, co-IP in Jurkat/COS cells, kinase and IL-2 reporter assays with kinase-dead epistasis

    PMID:11313918 PMID:11509653

    Open questions at the time
    • Single-lab functional assays
    • Apparent positive effect on IL-2 contrasts with negative regulatory role
  9. 2003 Medium

    Identified PGE2/GPCR signaling as a non-immunoreceptor input activating HPK1 to suppress fos transcription.

    Evidence PGE2 stimulation, kinase activity, and Fos reporter assays

    PMID:12522005

    Open questions at the time
    • Molecular mechanism of PGE2-induced activation not defined here
    • Single study
  10. 2004 High

    Provided structural definition of an atypical Gads SH3-binding mode on HPK1, explaining adaptor selectivity.

    Evidence ITC and X-ray crystallography of the HPK1 peptide·Mona/Gads SH3C complex

    PMID:15100220

    Open questions at the time
    • Structure of full-length adaptor·HPK1 complex not solved
    • Functional impact in cells not addressed
  11. 2005 High

    Demonstrated HPK1 is a bona fide component of the endogenous IKK complex required for TCR-driven NF-κB and that HPK1-C sequesters IKK to drive activation-induced cell death.

    Evidence siRNA knockdown, endogenous IKK co-IP, NF-κB reporters, and HPK1-C transgenic mice

    PMID:16341093

    Open questions at the time
    • Stoichiometry within IKK complex unresolved
    • Trigger generating HPK1-C physiologically not defined
  12. 2006 High

    Showed sub-apoptotic caspase-3 generates active HPK1-N to drive JNK-dependent progenitor survival and monocytic differentiation, giving cleavage a developmental role.

    Evidence Caspase inhibition and HPK1-N overexpression in primary mouse progenitors with JNK/Bad phosphorylation readouts

    PMID:17024227

    Open questions at the time
    • How sub-apoptotic caspase activity is restrained from killing the cell unclear
    • Direct HPK1-N substrates beyond JNK pathway not mapped
  13. 2007 High

    Defined two complementary roles for cleavage fragments in lymphocyte death and revealed PKA-dependent Ser171 phosphorylation as the mechanism of PGE2 activation.

    Evidence HPK1-C transgenic mice and siRNA for AICD; S171A mutagenesis and PKA-deficient S49 cells for PGE2 pathway

    PMID:17712048 PMID:17895239

    Open questions at the time
    • Connection between the PKA-Ser171 input and physiological outputs incompletely mapped
    • Selectivity of HPK1-C for anti-apoptotic Bcl-2 members mechanistically open
  14. 2008 Medium

    Implicated HPK1 in a Src→HPK1→MLK3→JNK3 cascade promoting ischemic neuronal death, extending its kinase circuitry beyond immune cells.

    Evidence Co-IP, pharmacological inhibition (PP2, MK801), and histology in rat hippocampus

    PMID:18498770

    Open questions at the time
    • Correlative in vivo epistasis without genetic loss-of-function
    • HPK1 expression/role in neurons not independently confirmed
  15. 2009 High

    Identified CARMA1 as a direct HPK1 substrate, providing the molecular link by which HPK1 promotes TCR-induced NF-κB and IL-2.

    Evidence In vitro kinase assay, CARMA1 site mutagenesis, and reconstitution in CARMA1-deficient T cells

    PMID:19706536

    Open questions at the time
    • How positive CARMA1 phosphorylation reconciles with overall negative regulation unresolved
    • Kinetics versus other HPK1 substrates not compared
  16. 2010 High

    Established HPK1 as a brake on integrin-mediated adhesion by competing with ADAP for SLP-76 and associating with SKAP-HOM to limit Rap1/LFA-1 activity in T and B cells.

    Evidence HPK1-deficient T and B cells, co-IP, Rap1 activation, and ICAM-1 adhesion assays

    PMID:20824186 PMID:20957749

    Open questions at the time
    • Whether kinase activity or scaffolding drives SLP-76 competition unclear
    • Direct phosphorylation targets in the adhesion module not all identified
  17. 2012 High

    Defined a degradative mechanism by which HPK1 dampens BCR signaling: BLNK Thr152 phosphorylation triggers 14-3-3 binding, ubiquitination, and degradation.

    Evidence HPK1-deficient B cells, in vitro kinase assay, BLNK mutagenesis, and ubiquitination assays

    PMID:22334673

    Open questions at the time
    • Ubiquitin ligase mediating BLNK degradation not identified
    • Generality to T-cell SLP-76 not tested
  18. 2013 High

    Showed HPK1 is required for chemokine-induced LFA-1 high-affinity adhesion and neutrophil extravasation in vivo, revealing a positive adhesion role in innate cells.

    Evidence HPK1-deficient mice, co-IP, confocal imaging, flow adhesion, and intravital microscopy

    PMID:23460610

    Open questions at the time
    • Opposite adhesion roles in lymphocytes versus neutrophils mechanistically unreconciled
    • Direct neutrophil substrates not defined
  19. 2019 High

    Provided the structural basis for HPK1 trans-regulation through phosphorylation-state-dependent dimer remodeling of the kinase domain.

    Evidence Multiple crystal structures of non-phosphorylated, doubly phosphorylated, and phosphomimetic kinase domains

    PMID:31018963

    Open questions at the time
    • In-cell relevance of the dimer interface not validated
    • Trigger of activation-loop autophosphorylation not structurally captured
  20. 2019 Medium

    Identified PDIA6 as an inhibitor of HPK1 phosphorylation that dampens JNK/c-Jun signaling and apoptosis in non-hematopoietic NSCLC cells.

    Evidence Co-IP, phospho-kinase array, and gain/loss-of-function in NSCLC cells

    PMID:30922965

    Open questions at the time
    • Direct versus indirect inhibition not distinguished
    • Single-lab non-hematopoietic context
  21. 2020 High

    Established HPK1 as a therapeutic target for antitumor immunity via an HPK1–NF-κB–Blimp1 axis driving T-cell dysfunction.

    Evidence MAP4K1 knockout mice, CAR-T tumor models, pharmacological inhibition, and PROTAC degradation

    PMID:32860752

    Open questions at the time
    • Direct HPK1 substrate in the Blimp1 axis not pinpointed
    • Catalytic versus scaffolding contribution to T-cell dysfunction unresolved
  22. 2021 High

    Revealed an innate-immune negative-regulatory function: HPK1 promotes DTX4-dependent K48-ubiquitination and degradation of TBK1/IKKε to limit interferon responses.

    Evidence Yeast two-hybrid, co-IP, ubiquitination assays, knockdown/knockout, and IFN-β reporters

    PMID:34908452

    Open questions at the time
    • Whether HPK1 kinase activity is required for DTX4 recruitment unclear
    • Single-lab characterization
  23. 2022 Medium

    Characterized a druggable allosteric pocket outside the kinase domain and an integrin-induced HPK1 signaling cluster, refining inhibitor strategy and interactome.

    Evidence ATP-noncompetitive allosteric inhibitor binding assays; co-IP/MS interactome of HL-60 cells with DAP12/Syk/Rac1

    PMID:34608799 PMID:35099066

    Open questions at the time
    • Allosteric binding site not structurally resolved
    • Functional validation of most interactome members lacking
  24. 2024 High

    Defined the citron homology domain structure and its autoinhibitory, substrate-docking, and stabilizing functions, completing the intramolecular regulatory picture.

    Evidence CHD crystal structure, HDX-MS, CHD–KD mutagenesis, kinase assays, co-IP, and stability assays

    PMID:38697971

    Open questions at the time
    • How adaptor binding relieves CHD autoinhibition not shown
    • Conformational coupling between CHD and dimer remodeling unexplored
  25. 2024 Medium

    Extended HPK1's immunosuppressive role to NK cells, where aberrant overexpression restrains cytotoxicity and promotes metastasis.

    Evidence Conditional NK overexpression and MAP4K1-deficient mice with cytotoxicity and metastasis assays

    PMID:38828677

    Open questions at the time
    • NK-specific substrates not identified
    • TGF-β1 linkage mechanistically incomplete
  26. 2025 Medium

    Identified HPK1 as a driver of pathological neutrophil hyperactivation and mobilization after ischemic stroke.

    Evidence HPK1 loss-of-function mice, pharmacological inhibition, and MCAO stroke model with NF-κB/STAT3/p38 and gasdermin D readouts

    PMID:40169896

    Open questions at the time
    • Direct HPK1 substrates in neutrophil pyroptosis/NET pathway not defined
    • Single-lab study

Open questions

Synthesis pass · forward-looking unresolved questions
  • How HPK1 reconciles opposing roles (NF-κB/CARMA1 activation versus AP-1/adhesion suppression; lymphocyte versus neutrophil adhesion) and how adaptor engagement relieves CHD/dimer autoinhibition to direct catalysis toward specific substrates remains unresolved.
  • No unified model linking conformational state to substrate choice
  • Catalytic versus scaffolding contributions across contexts not systematically dissected

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 5 GO:0140096 catalytic activity, acting on a protein 3 GO:0060089 molecular transducer activity 2 GO:0140657 ATP-dependent activity 2
Localization
GO:0005829 cytosol 2 GO:0005856 cytoskeleton 1
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-168256 Immune System 4 R-HSA-5357801 Programmed Cell Death 4 R-HSA-392499 Metabolism of proteins 2
Partners
BLNKCARMA1CRKLGADS/GRAP2GRB2MEKK1SLP-76TBK1
Complex memberships
IKK complex

Evidence

Reading pass · 32 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 HPK1 (MAP4K1) is a Ste20-related serine/threonine kinase that directly binds and phosphorylates MEKK1, and activates JNK1 specifically; JNK1 activation by HPK1 is inhibited by dominant-negative MEKK1 or MKK4/SEK1 mutants, placing HPK1 upstream of MEKK1→MKK4→JNK1 in the JNK/SAPK pathway. Unlike PAK65, HPK1 does not bind Rac1 or Cdc42, indicating Rac1/Cdc42-independent activation. Transient transfection assays with dominant-negative mutants, direct in vitro binding and phosphorylation assay Genes & development High 8824585 9003777
1996 HPK1 specifically activates the SAPK/JNK pathway but not p38/RK or ERK; activation requires a functional HPK1 kinase domain and proceeds via the mixed lineage kinase MLK-3 and the SAPK activator SEK1. Transfection in COS1 cells with kinase-inactive mutants and dominant-negative pathway components The EMBO journal High 9003777
1997 TAK1 acts downstream of HPK1 and upstream of MKK4/SEK1 in a HPK1→TAK1→MKK4/SEK1→JNK kinase cascade; a kinase-defective TAK1 mutant suppressed HPK1-induced JNK activity, while dominant-negative MEKK1 and MLK3 did not inhibit TAK1-induced JNK, indicating TAK1 is an alternative HPK1 downstream effector independent of MEKK1/MLK3. Transient transfection assays with dominant-negative and constitutively active mutants of TAK1, MEKK1, MLK3, and MKK4/SEK1 The Journal of biological chemistry High 9278437
1997 The SH3 domains of Grb2 bind to specific proline-rich motifs in the HPK1 C-terminal tail, forming a stable Grb2·HPK1 complex in transfected cells. EGF stimulation recruits the Grb2·HPK1 complex to the autophosphorylated EGF receptor and to Shc. Multiple activated receptor and cytoplasmic tyrosine kinases (including EGFR) stimulate tyrosine phosphorylation of HPK1, demonstrating SH2/SH3 adaptor-mediated cross-talk between tyrosine kinase and HPK1 pathways. In vitro SH3-domain binding assay, co-immunoprecipitation in transfected COS1 cells, EGF stimulation experiments The Journal of biological chemistry High 9346925
1998 HPK1 binds selectively to the first SH3 domains of c-Crk and CRKL via proline-rich motifs in its C-terminal non-catalytic portion; in vitro and in vivo Crk/CRKL–HPK1 complexes were detected by co-immunoprecipitation. HPK1 phosphorylates c-Crk II and CRKL in vitro, suggesting HPK1 can regulate adaptor protein function downstream. In vitro SH3-domain binding assays with >25 SH3 domains, co-immunoprecipitation of endogenous proteins, in vitro kinase assay Oncogene High 9788432
1999 HPK1 is cleaved by caspase-3 during apoptosis at the conserved DDVD site (Asp385), separating the N-terminal kinase domain from the C-terminal regulatory domain. Caspase-3 cleavage enhances HPK1 kinase activity. The N-terminal cleavage product fails to bind adaptors Grb2 and Crk, while the C-terminal fragment binds them less efficiently than full-length HPK1. In vitro caspase-3 cleavage assay, site-directed mutagenesis of Asp385, in vivo/in vitro cleavage assays, co-immunoprecipitation Oncogene High 10602493
1999 HPK1 activates both IKK-alpha and IKK-beta, which phosphorylate IκB constitutively (IKK-beta) or upon stimulation (IKK-alpha), placing HPK1 upstream of the IκB/NF-κB pathway via a HPK1–MEKK1 stress response signaling pathway. Transient transfection with HPK1 and MEKK1 constructs, IKK kinase activity assays Oncogene Medium 10523828
2000 TCR or BCR engagement induces HPK1 catalytic activity; Src and Syk/ZAP-70 tyrosine kinases and adaptor proteins LAT, SLP-76, BLNK, Grb2, and Grap are required for HPK1 activation. Overexpression of HPK1 inhibits TCR-induced AP-1 and ERK2 activation, while kinase-inactive HPK1 potentiates these responses, establishing HPK1 as a negative regulator of the TCR-induced AP-1 pathway. Antigen receptor stimulation assays, overexpression and kinase-inactive mutant transfections in T and B cells Immunity High 10795738
2001 Caspase-mediated cleavage of HPK1 converts it from an activator to an inhibitor of NF-κB. Full-length, kinase-active HPK1 activates NF-κB via IKKβ (independently of SAPK/JNK); the isolated kinase domain activates SAPK/JNK but not NF-κB. The C-terminal cleavage fragment (HPK1-C) inhibits NF-κB by dominant-negative mechanism, blocking NIK- and TNFα-mediated NF-κB activation, suggesting impairment of the IKK complex. Dominant-negative IKKβ cotransfection, overexpression of HPK1 truncation fragments, NF-κB reporter assays in myeloid progenitor cells The Journal of biological chemistry High 11278403
2001 Grap2 (GADS) interacts with HPK1 via its C-terminal SH3 domain binding to the second proline-rich motif of HPK1 in vitro and in Jurkat T cells. Coexpression of Grap2 with HPK1 increases HPK1 kinase activity and has an additive effect on JNK activation, and promotes IL-2 gene transcription. In vitro binding assay, co-immunoprecipitation in Jurkat T cells, kinase activity assay, IL-2 reporter assay Oncogene Medium 11313918
2001 Clnk (a SLP-76 family adaptor) physically and functionally interacts with HPK1 in hematopoietic cells; their interaction is augmented by immunoreceptor stimulation. Clnk and HPK1 cooperate to increase IL-2 promoter activity, and kinase-defective HPK1 blocks Clnk-mediated IL-2 induction, demonstrating functional dependence on HPK1 kinase activity. Yeast two-hybrid screen, cotransfection in COS-1 cells, IL-2 reporter assay in Jurkat T cells, kinase-dead HPK1 epistasis Molecular and cellular biology Medium 11509653
2003 PGE2 activates HPK1 catalytic activity in hematopoietic cells, and ectopic HPK1 expression negatively regulates PGE2-induced fos gene transcription, establishing HPK1 as a negative regulator downstream of PGE2/GPCR signaling. PGE2 stimulation assays, HPK1 kinase activity measurements, ectopic expression studies with Fos reporter assays Blood Medium 12522005
2004 The Mona/Gads C-terminal SH3 domain binds HPK1 via an atypical combined RXXK + PXXP motif; crystal structure of the complex at molecular resolution shows that an RXXK charge interaction is essential and a PXXP motif strongly complements binding, defining an unusual SH3-binding mode distinct from Mona/Gads·SLP-76 interaction. Isothermal titration calorimetry, X-ray crystallography of the HPK1-peptide/Mona-Gads SH3C complex The Journal of biological chemistry High 15100220
2005 HPK1 is a functional component of the endogenous IKK complex and is required for TCR-mediated NF-κB activation; full-length HPK1 enhances IKKβ phosphorylation. siRNA knockdown of HPK1 blunts TCR-mediated NF-κB activation and increases T-cell death. HPK1-C (caspase cleavage product) sequesters the inactive IKK complex and suppresses NF-κB by binding IKKα and IKKβ, sensitizing T cells to activation-induced cell death (AICD). HPK1-C transgenic mice show enhanced TCR-mediated AICD. siRNA knockdown, co-immunoprecipitation with endogenous IKK complex, NF-κB reporter assays, transgenic mouse model, IKKβ phosphorylation assay The EMBO journal High 16341093
2006 During monocytic differentiation, HPK1 is proteolytically processed by sub-apoptotic caspase-3 to generate a constitutively active N-terminal kinase fragment (HPK1-N) that drives sustained JNK activation, Bad phosphorylation, IL-3-independent progenitor cell survival, and monocytic lineage commitment. Blocking caspase activity reduces HPK1-N levels, suppresses JNK, and attenuates monocytic differentiation. Caspase inhibitor treatment of primary mouse progenitor cells, HPK1-N overexpression, JNK and Bad phosphorylation assays, cell survival and differentiation analysis Cell death and differentiation High 17024227
2007 HPK1-C (caspase cleavage product) generated by sub-apoptotic caspase-3 activity in IL-2-expanded T cells selectively blocks NF-κB-dependent anti-apoptotic Bcl-2 family members but not pro-apoptotic Bim, inducing CD95L-independent AICD involving caspase-9. This pathway complements CD95L-dependent AICD in primary T and B lymphocytes. HPK1-C transgenic mice, siRNA knockdown of HPK1/Bim, primary T and B cell apoptosis assays Blood High 17712048
2007 PGE2 activates HPK1 kinase via a PKA-dependent pathway: changing Ser171 (an optimal PKA phosphorylation site in the activation loop) to Ala completely prevents HPK1 from responding to PGE2. HPK1 activation by PGE2 does not require phosphotyrosine-based signaling molecules (Lck, ZAP-70, SLP-76, Lat) or proline-rich/SH3-domain interactions required for TCR-induced HPK1 activation. PKA-deficient S49 cells fail to activate HPK1 in response to PGE2. Site-directed mutagenesis (S171A), PKA-deficient S49 cell line, HPK1 kinase activity assays The Journal of biological chemistry High 17895239
2009 HPK1 phosphorylates the linker region of CARMA1 at residues S549, S551, and S552 (different from PKC consensus sites) in a TCR stimulation-dependent interaction. Mutations S551A or S549A/S551A abrogated CARMA1 phosphorylation by HPK1 in vitro and failed to restore HPK1-mediated and TCR-mediated NF-κB activation and IL-2 expression in CARMA1-deficient T cells. In vitro kinase assay with HPK1 and CARMA1-linker construct, site-directed mutagenesis of CARMA1, co-immunoprecipitation, NF-κB reporter assay and IL-2 expression in CARMA1-deficient T cells Proceedings of the National Academy of Sciences of the United States of America High 19706536
2010 HPK1 competes with ADAP for SLP-76 binding upon TCR stimulation. HPK1 dampens Rap1 activation, resulting in decreased LFA-1 integrin activity. HPK1-deficient T cells show increased ADAP recruitment to SLP-76, elevated Rap1 activation, and increased adhesion to ICAM-1 and cell spreading. Co-immunoprecipitation, HPK1-deficient mouse T cells, Rap1 activation assay, ICAM-1 adhesion assay European journal of immunology High 20957749
2010 HPK1 associates with SKAP-HOM in B cells; HPK1 loss leads to increased Rap1 activation, LFA-1-dependent homotypic aggregation, and increased ICAM-1 adhesion. This is downstream of Src, independent of PI3K and PLC, involving HPK1, SKAP-HOM, and RIAM, and alters actin dynamics with constitutive FAK phosphorylation. shRNA knockdown in WEHI231 cells, HPK1(-/-) mouse B cells, Rap1 activation assay, adhesion assay, FAK phosphorylation assay PloS one Medium 20824186
2012 HPK1 phosphorylates BLNK at threonine 152 upon BCR activation, inducing BLNK/14-3-3 binding. Thr152-phosphorylated BLNK is ubiquitinated at lysines 37, 38, and 42, leading to BLNK degradation and attenuation of MAPK (ERK, p38, JNK) and IKK activation in B cells. HPK1-deficient B cells display hyper-proliferation and hyper-activation of IκB kinase and MAPKs. HPK1-deficient B cells, in vitro kinase/phosphorylation assay, co-immunoprecipitation, site-directed mutagenesis of BLNK (T152), ubiquitination assay The Journal of biological chemistry High 22334673
2013 HPK1 is required for CXCL1-induced LFA-1-mediated neutrophil adhesion to ICAM-1 under flow conditions, and for LFA-1 high-affinity conformation induction. HPK1 co-localizes with mAbp1 and actin at the lamellipodium of polarized neutrophil-like cells. HPK1-deficient mice show severely compromised neutrophil adhesion and extravasation upon TNFα treatment in vivo. Co-immunoprecipitation in HL-60 cells, confocal microscopy (HPK1 localization), HPK1-deficient mouse PMN adhesion assays under flow, intravital microscopy Blood High 23460610
2019 Crystal structures of the HPK1 kinase domain in non-phosphorylated and doubly phosphorylated states (complexed with sunitinib) at 2.17–3.00 Å resolution reveal: (1) the non-phosphorylated kinase forms an inactive dimer in which the activation loop of each monomer partially occupies the ATP- and substrate-binding sites of the partner; (2) the doubly phosphorylated activation loop adopts an active kinase conformation with reduced dimer interface; (3) a phosphomimetic double mutant (T165E, S171E) exhibits an alternative domain-swapped configuration. HPK1 undergoes trans-regulation via dimer formation and activation-loop remodeling. X-ray crystallography (multiple structures), phosphorylation-state mutant constructs The Journal of biological chemistry High 31018963
2019 PDIA6 interacts with MAP4K1 (HPK1) by co-immunoprecipitation and inhibits HPK1 phosphorylation, leading to reduced JNK/c-Jun signaling and decreased cisplatin-induced apoptosis in NSCLC cells. Co-immunoprecipitation, human phospho-kinase array, gain- and loss-of-function overexpression/knockdown experiments EBioMedicine Medium 30922965
2020 HPK1 mediates T cell dysfunction via an HPK1–NF-κB–Blimp1 axis. MAP4K1 knockout mice show slower tumor growth with less exhausted, more active, and more proliferative tumor-infiltrating T cells. Pharmacological inhibition or PROTAC-mediated degradation of HPK1 improves CAR-T cell efficacy in preclinical tumor models. MAP4K1 knockout mice, CAR-T adoptive transfer tumor models, pharmacological inhibition, PROTAC degradation Cancer cell High 32860752
2021 MAP4K1 acts as a negative regulator in the RLR (RIG-I-like receptor) innate immune signaling pathway by promoting K48-linked ubiquitination and proteasomal degradation of TBK1 and IKKε via the ubiquitin ligase DTX4. MAP4K1 was identified as an interacting partner of TBK1 by yeast two-hybrid; overexpression inhibits RNA-virus-triggered IFN-β and pro-inflammatory cytokine production; knockdown/knockout has opposite effects; DTX4 knockdown abrogates TBK1/IKKε ubiquitination and degradation. Yeast two-hybrid screen, co-immunoprecipitation, overexpression and knockdown/knockout assays, K48-linked ubiquitination assay, IFN-β reporter assay Microbiology spectrum High 34908452
2022 An allosteric, inactive-conformation-selective HPK1 inhibitor (triazolopyrimidinone compound 1) binds unphosphorylated HPK1 >24-fold more potently than active HPK1, is not competitive with ATP, requires domains outside the isolated kinase domain for binding, and attenuates HPK1 autophosphorylation. This demonstrates that HPK1 has a druggable allosteric pocket outside the kinase domain. Cascade kinase assay, ATP competition assay, binding assays with isolated KD vs. full-length protein, selectivity profiling Biochemistry Medium 34608799
2024 The citron homology domain (CHD) of HPK1 adopts a seven-bladed β-propellor fold and directly binds the HPK1 kinase domain (KD). Mutagenesis studies show a direct correlation between CHD–KD interaction and negative regulation of kinase activity. The CHD also contributes to docking of the substrate SLP76 and provides stability to HPK1 protein in cells. X-ray crystallography (CHD structure), hydrogen-deuterium exchange mass spectrometry, CHD–KD binding mutagenesis, functional kinase activity assays, co-immunoprecipitation, cellular stability assays Nature communications High 38697971
2024 HPK1 aberrantly overexpressed in NK cells restrains NK cell cytotoxicity and expansion via activating receptors; conditional HPK1 overexpression in NK cells exacerbates melanoma lung metastasis while MAP4K1-deficient mice are resistant to metastasis. HPK1 limits human NK cell activation and is associated with melanoma NK cell dysfunction coupled to TGF-β1. Conditional HPK1 overexpression in NK cells (in vivo mouse model), MAP4K1-deficient mice, NK cell cytotoxicity assays, in vitro activation assays Advanced science Medium 38828677
2025 HPK1 promotes neutrophil mobilization, LPS-induced neutrophil activation, NF-κB/STAT3/p38-MAPK pathway activation, and gasdermin D cleavage. Following acute ischemic stroke, HPK1 promotes CXCR2high bone marrow neutrophil mobilization. HPK1 loss inhibits peripheral neutrophil hyperactivation, neutrophil extracellular trap aggregation, and alleviates post-stroke pulmonary and neurological injuries. HPK1 loss-of-function mouse model, pharmacological HPK1 inhibition, neutrophil activation assays, stroke model (MCAO), pathway analysis (NF-κB/STAT3/p38) EMBO molecular medicine Medium 40169896
2008 In rat hippocampus after cerebral ischemia/reperfusion, activated Src tyrosine-phosphorylates HPK1, which then activates the downstream MLK3–MKK7–JNK3 pathway, promoting ischemic neuron death. PP2 (Src inhibitor) and MK801 (NMDA receptor antagonist) reduce activation of Src, HPK1, MLK3, JNK3, and c-Jun and protect against neuron death. Co-immunoprecipitation and immunoblot in rat hippocampal CA1, pharmacological inhibition (PP2, MK801), histology and TUNEL staining FEBS letters Medium 18498770
2022 In neutrophil-like HL-60 cells, HPK1 exists in a pre-assembled signaling cluster with DAP12, Syk, and Rac1; activation by β2 integrin-mediated adhesion changes the composition of the HPK1-interacting proteome (identified 115 interacting proteins by co-IP/MS, with 58 unique to non-activated and 39 unique to Mn2+-activated conditions). Co-immunoprecipitation followed by mass spectrometry (proteomics), two adhesion states (non-activated vs Mn2+-activated HL-60 cells) European journal of immunology Medium 35099066

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1996 Human HPK1, a novel human hematopoietic progenitor kinase that activates the JNK/SAPK kinase cascade. Genes & development 222 8824585
1996 HPK1, a hematopoietic protein kinase activating the SAPK/JNK pathway. The EMBO journal 205 9003777
1997 Activation of the hematopoietic progenitor kinase-1 (HPK1)-dependent, stress-activated c-Jun N-terminal kinase (JNK) pathway by transforming growth factor beta (TGF-beta)-activated kinase (TAK1), a kinase mediator of TGF beta signal transduction. The Journal of biological chemistry 169 9278437
2020 Hematopoietic Progenitor Kinase1 (HPK1) Mediates T Cell Dysfunction and Is a Druggable Target for T Cell-Based Immunotherapies. Cancer cell 162 32860752
2000 HPK1 is activated by lymphocyte antigen receptors and negatively regulates AP-1. Immunity 116 10795738
2019 PDIA6 modulates apoptosis and autophagy of non-small cell lung cancer cells via the MAP4K1/JNK signaling pathway. EBioMedicine 85 30922965
1997 SH2/SH3 adaptor proteins can link tyrosine kinases to a Ste20-related protein kinase, HPK1. The Journal of biological chemistry 74 9346925
2021 Enhanced antitumor immunity by a novel small molecule HPK1 inhibitor. Journal for immunotherapy of cancer 71 33408094
1999 Caspase-mediated cleavage and functional changes of hematopoietic progenitor kinase 1 (HPK1). Oncogene 70 10602493
2001 Caspase-mediated cleavage of hematopoietic progenitor kinase 1 (HPK1) converts an activator of NFkappaB into an inhibitor of NFkappaB. The Journal of biological chemistry 66 11278403
2005 Activation or suppression of NFkappaB by HPK1 determines sensitivity to activation-induced cell death. The EMBO journal 64 16341093
2004 Mona/Gads SH3C binding to hematopoietic progenitor kinase 1 (HPK1) combines an atypical SH3 binding motif, R/KXXK, with a classical PXXP motif embedded in a polyproline type II (PPII) helix. The Journal of biological chemistry 61 15100220
2020 A perspective on HPK1 as a novel immuno-oncology drug target. eLife 59 32896273
2012 Down-regulation of B cell receptor signaling by hematopoietic progenitor kinase 1 (HPK1)-mediated phosphorylation and ubiquitination of activated B cell linker protein (BLNK). The Journal of biological chemistry 52 22334673
2009 Phosphorylation of CARMA1 by HPK1 is critical for NF-kappaB activation in T cells. Proceedings of the National Academy of Sciences of the United States of America 52 19706536
2011 hsa-miR-96 up-regulates MAP4K1 and IRS1 and may function as a promising diagnostic marker in human bladder urothelial carcinomas. Molecular medicine reports 51 21993544
1998 The germinal center kinase (GCK)-related protein kinases HPK1 and KHS are candidates for highly selective signal transducers of Crk family adapter proteins. Oncogene 51 9788432
2022 The development of small-molecule inhibitors targeting HPK1. European journal of medicinal chemistry 50 36209628
2012 HPK1 as a novel target for cancer immunotherapy. Immunologic research 50 22477524
2001 Leukocyte-specific adaptor protein Grap2 interacts with hematopoietic progenitor kinase 1 (HPK1) to activate JNK signaling pathway in T lymphocytes. Oncogene 50 11313918
2005 Functional interactions of HPK1 with adaptor proteins. Journal of cellular biochemistry 46 15770651
2021 Discovery of Diaminopyrimidine Carboxamide HPK1 Inhibitors as Preclinical Immunotherapy Tool Compounds. ACS medicinal chemistry letters 43 33859804
2021 Inhibitors of immuno-oncology target HPK1 - a patent review (2016 to 2020). Expert opinion on therapeutic patents 43 33956554
2001 Synergistic regulation of immunoreceptor signaling by SLP-76-related adaptor Clnk and serine/threonine protein kinase HPK-1. Molecular and cellular biology 43 11509653
2022 Discovery of Macrocycle-Based HPK1 Inhibitors for T-Cell-Based Immunotherapy. Journal of medicinal chemistry 41 36542759
2007 Caspase-cleaved HPK1 induces CD95L-independent activation-induced cell death in T and B lymphocytes. Blood 40 17712048
1999 Hematopoietic progenitor kinase-1 (HPK1) stress response signaling pathway activates IkappaB kinases (IKK-alpha/beta) and IKK-beta is a developmentally regulated protein kinase. Oncogene 40 10523828
2021 Discovery of Spiro-azaindoline Inhibitors of Hematopoietic Progenitor Kinase 1 (HPK1). ACS medicinal chemistry letters 38 35059127
2007 Prostaglandin E2 activates HPK1 kinase activity via a PKA-dependent pathway. The Journal of biological chemistry 37 17895239
2017 The homeodomain-interacting protein kinase HPK-1 preserves protein homeostasis and longevity through master regulatory control of the HSF-1 chaperone network and TORC1-restricted autophagy in Caenorhabditis elegans. PLoS genetics 36 29036198
2022 The HPK1 Inhibitor A-745 Verifies the Potential of Modulating T Cell Kinase Signaling for Immunotherapy. ACS chemical biology 35 35188729
2021 Identification of Potent Reverse Indazole Inhibitors for HPK1. ACS medicinal chemistry letters 34 33738073
2012 Pdcd4 knockdown up-regulates MAP4K1 expression and activation of AP-1 dependent transcription through c-Myc. Biochimica et biophysica acta 33 22801218
2006 Sustained JNK signaling by proteolytically processed HPK1 mediates IL-3 independent survival during monocytic differentiation. Cell death and differentiation 33 17024227
2021 SPIB acts as a tumor suppressor by activating the NFkB and JNK signaling pathways through MAP4K1 in colorectal cancer cells. Cellular signalling 32 34530056
2003 Hematopoietic progenitor kinase 1 (HPK1) negatively regulates prostaglandin E2-induced fos gene transcription. Blood 31 12522005
2019 DLX6-AS1 promotes cell proliferation, migration and EMT of gastric cancer through FUS-regulated MAP4K1. Cancer biology & therapy 30 31591939
2019 Multiple conformational states of the HPK1 kinase domain in complex with sunitinib reveal the structural changes accompanying HPK1 trans-regulation. The Journal of biological chemistry 26 31018963
2013 Hematopoietic progenitor kinase 1 (HPK1) is required for LFA-1-mediated neutrophil recruitment during the acute inflammatory response. Blood 25 23460610
2023 Design, Synthesis, and Pharmacological Evaluation of Isoindoline Analogues as New HPK1 Inhibitors. Journal of medicinal chemistry 24 37990878
2024 Discovery of Pyridine-2-Carboxamides Derivatives as Potent and Selective HPK1 Inhibitors for the Treatment of Cancer. Journal of medicinal chemistry 22 39585942
2019 Long noncoding RNA CDKN2B-AS1 interacts with transcription factor BCL11A to regulate progression of cerebral infarction through mediating MAP4K1 transcription. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 22 30870006
2023 Discovery of highly efficient CRBN-recruiting HPK1-PROTAC as a potential chemical tool for investigation of scaffolding roles in TCR signaling. Bioorganic chemistry 21 38086239
2022 Development of a series of quinazoline-2,5-diamine derivatives as potent hematopoietic progenitor kinase 1 (HPK1) inhibitors. European journal of medicinal chemistry 21 36621137
2024 Discovery of an Exceptionally Orally Bioavailable and Potent HPK1 PROTAC with Enhancement of Antitumor Efficacy of Anti-PD-L1 Therapy. Journal of medicinal chemistry 20 39084610
2023 Discovery of 7H-Pyrrolo[2,3-d]pyrimidine Derivatives as potent hematopoietic progenitor kinase 1 (HPK1) inhibitors. European journal of medicinal chemistry 20 37062169
2010 HPK1 competes with ADAP for SLP-76 binding and via Rap1 negatively affects T-cell adhesion. European journal of immunology 20 20957749
2020 HPK1 Influences Regulatory T Cell Functions. ImmunoHorizons 19 32631900
2019 The Structure of HPK1 Kinase Domain: To Boldly Go Where No Immuno-Oncology Drugs Have Gone Before. Structure (London, England : 1993) 19 30605659
2010 HPK1 associates with SKAP-HOM to negatively regulate Rap1-mediated B-lymphocyte adhesion. PloS one 19 20824186
2024 Discovery of novel, potent, selective and orally bioavailable HPK1 inhibitor for enhancing the efficacy of anti-PD-L1 antibody. European journal of medicinal chemistry 18 38350360
2024 Current strategies for targeting HPK1 in cancer and the barriers to preclinical progress. Expert opinion on therapeutic targets 17 38650383
2024 Discovery of PF-07265028, A Selective Small Molecule Inhibitor of Hematopoietic Progenitor Kinase 1 (HPK1) for the Treatment of Cancer. Journal of medicinal chemistry 17 39651809
2023 Highly potent, orally active novel small-molecule HPK1 inhibitor DS21150768 induces anti-tumor responses in multiple syngeneic tumor mouse models. European journal of pharmacology 16 37944847
2021 MAP4K1 functions as a tumor promotor and drug mediator for AML via modulation of DNA damage/repair system and MAPK pathway. EBioMedicine 16 34166980
2021 Discovery of an Allosteric, Inactive Conformation-Selective Inhibitor of Full-Length HPK1 Utilizing a Kinase Cascade Assay. Biochemistry 16 34608799
2016 Homeodomain-Interacting Protein Kinase (HPK-1) regulates stress responses and ageing in C. elegans. Scientific reports 16 26791749
2025 Discovery and Optimization of Pyrazine Carboxamide AZ3246, a Selective HPK1 Inhibitor. Journal of medicinal chemistry 15 39928839
2021 The Kinase MAP4K1 Inhibits Cytosolic RNA-Induced Antiviral Signaling by Promoting Proteasomal Degradation of TBK1/IKKε. Microbiology spectrum 15 34908452
2024 Discovery of BAY-405: An Azaindole-Based MAP4K1 Inhibitor for the Enhancement of T-Cell Immunity against Cancer. Journal of medicinal chemistry 14 39331123
2023 Discovery of potent and selective HPK1 inhibitors based on the 2,4-disubstituted pyrimidine scaffold with immune modulatory properties for ameliorating T cell exhaustion. Bioorganic chemistry 14 37536217
2022 Discovery of Novel HPK1 Inhibitors Through Structure-Based Virtual Screening. Frontiers in pharmacology 14 35370676
2024 Discovery of Novel PROTAC-Based HPK1 Degraders with High Potency and Selectivity for Cancer Immunotherapy. Journal of medicinal chemistry 13 39446986
2012 The pan-caspase inhibitor Q-VD-OPh has anti-leukemia effects and can interact with vitamin D analogs to increase HPK1 signaling in AML cells. Leukemia research 13 22541691
2024 HPK1 citron homology domain regulates phosphorylation of SLP76 and modulates kinase domain interaction dynamics. Nature communications 12 38697971
2024 HPK1 Dysregulation-Associated NK Cell Dysfunction and Defective Expansion Promotes Metastatic Melanoma Progression. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 12 38828677
2024 Discovery of GNE-6893, a Potent, Selective, Orally Bioavailable Small Molecule Inhibitor of HPK1. ACS medicinal chemistry letters 12 39291002
2023 An HPK1 inhibitor enhanced the tumour response to anti-PD-1 immunotherapy in non-Hodgkin's lymphoma. Clinical and experimental medicine 12 37106265
2023 Discovery of quinazoline HPK1 inhibitors with high cellular potency. Bioorganic & medicinal chemistry 12 37531921
2023 Design and synthesis of 1H-pyrazolo[3,4-d]pyrimidine derivatives as hematopoietic progenitor kinase 1 (HPK1) inhibitors. Bioorganic chemistry 12 37659145
2022 Discovery of Pyrazolopyridine Derivatives as HPK1 Inhibitors. ACS medicinal chemistry letters 12 36655125
2020 Using yeast surface display to engineer a soluble and crystallizable construct of hematopoietic progenitor kinase 1 (HPK1). Acta crystallographica. Section F, Structural biology communications 12 33439152
2024 Opportunities and challenges for targeting HPK1 in cancer immunotherapy. Bioorganic chemistry 11 39369461
2022 Potent and Selective Biaryl Amide Inhibitors of Hematopoietic Progenitor Kinase 1 (HPK1). ACS medicinal chemistry letters 11 36655134
2013 Homeodomain interacting protein kinase (HPK-1) is required in the soma for robust germline proliferation in C. elegans. Developmental dynamics : an official publication of the American Association of Anatomists 11 23904186
2012 Dual role of hematopoietic progenitor kinase 1 (HPK1) as a positive regulator of 1α,25-dihydroxyvitamin D-induced differentiation and cell cycle arrest of AML cells and as a mediator of vitamin D resistance. Cell cycle (Georgetown, Tex.) 11 22421156
2024 Design, synthesis, and biological evaluation of 2,4-diaminopyrimidine derivatives as potent Hematopoietic Progenitor Kinase 1 (HPK1) inhibitors. Bioorganic chemistry 10 38795581
2024 Design, Synthesis, and Biological Evaluation of a Series of Spiro Analogues as Novel HPK1 Inhibitors. ACS medicinal chemistry letters 10 39563821
2023 Glioblastoma cellular MAP4K1 facilitates tumor growth and disrupts T effector cell infiltration. Life science alliance 10 37734869
2024 Discovery of 5-aminopyrido[2,3-d]pyrimidin-7(8H)-one derivatives as new hematopoietic progenitor kinase 1 (HPK1) inhibitors. European journal of medicinal chemistry 9 38479166
2024 Discovery of 1(2H)-phthalazinone and 1(2H)-isoquinolinone derivatives as potent hematopoietic progenitor kinase 1 (HPK1) inhibitors. European journal of medicinal chemistry 9 39303515
2025 Discovery of 1,2,4-benzotriazine derivatives as new hematopoietic progenitor kinase 1 (HPK1) inhibitors. Bioorganic chemistry 8 39826501
2018 Identification of proteins regulated by acid adaptation related two component system HPK1/RR1 in Lactobacillus delbrueckii subsp. bulgaricus. Archives of microbiology 7 30022229
2025 Design, Synthesis, and biological evaluation of 7H-Pyrrolo[2,3-d]pyrimidines as potent HPK1 kinase inhibitors. Bioorganic & medicinal chemistry 6 39874881
2024 Design, synthesis, and biological evaluation of novel HPK1 inhibitors possessing 3-cyano-quinoline moiety. Bioorganic chemistry 6 39299176
2024 An updated review of small-molecule HPK1 kinase inhibitors (2016-present). Future medicinal chemistry 6 39582317
2024 Pharmacological inhibition of HPK1 synergizes with PD-L1 blockade to provoke antitumor immunity against tumors with low antigenicity. Biochemical and biophysical research communications 5 38685185
2025 HPK1 kinase inhibitor: a sufficient approach to target HPK1 to modulate T cell activation in cancer immunotherapy compared with degraders. Frontiers in immunology 4 39981246
2025 Highly selective HPK1 inhibitor NDI-101150 mediates immune cell activation and robust antitumor responses, distinct from immune checkpoint blockade. Journal for immunotherapy of cancer 4 40738502
2025 Discovery of a Novel Potent and Orally Efficacious PROTAC Degrader of HPK1 for Tumor Immunotherapy. Journal of medicinal chemistry 4 40738757
2008 Tyrosine phosphorylation of HPK1 by activated Src promotes ischemic brain injury in rat hippocampal CA1 region. FEBS letters 4 18498770
2025 Updated patent review for hematopoietic progenitor kinase (HPK1) inhibitors and degraders (2021-present). Expert opinion on therapeutic patents 3 39950624
2023 Theoretical Studies on Selectivity of HPK1/JAK1 Inhibitors by Molecular Dynamics Simulations and Free Energy Calculations. International journal of molecular sciences 3 36768974
2015 [Interactions between MAP4K1 and adaptor proteins]. Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences 3 25832533
2025 CBX2 as a therapeutic target in colorectal cancer: insights into the altered chromatin accessibility via RUNX1-CBX2-MAP4K1 axis. Oncogene 2 40082555
2025 Targeting HPK1 inhibits neutrophil responses to mitigate post-stroke lung and cerebral injuries. EMBO molecular medicine 2 40169896
2025 Design, synthesis and structure-activity relationship studies of novel macrocyclic 2,4-diaminopyrimidines as HPK1 inhibitors. Bioorganic & medicinal chemistry 2 40494219
2025 Design, synthesis, and biological evaluation of 2-substituted-pyridin-4-yl macrocyclic derivatives as new selective HPK1 inhibitors. Bioorganic chemistry 2 40902512
2022 Decoding the signaling profile of hematopoietic progenitor kinase 1 (HPK1) in innate immunity: A proteomic approach. European journal of immunology 2 35099066
2013 Gimme a brake: HPK1 regulates LFA-1 and neutrophil traction. Blood 2 23682030

Missed literature

Know a paper Affinage missed for MAP4K1? Flag it for the maintainers and the community.

No submissions yet.