Affinage

CSK

Tyrosine-protein kinase CSK · UniProt P41240

Length
450 aa
Mass
50.7 kDa
Annotated
2026-06-09
100 papers in source corpus 47 papers cited in narrative 46 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

CSK is a cytosolic non-receptor tyrosine kinase that functions as the master negative regulator of Src-family kinases (SFKs), phosphorylating their conserved C-terminal regulatory tyrosine (e.g., Lyn Tyr508, Src Tyr529) to repress kinase activity and lock SFKs in an inactive conformation (PMID:1722201, PMID:11940607). CSK preferentially acts on SFKs that are already activation-loop autophosphorylated and accessible: autophosphorylated, dimerized Src/Lck are favored substrates, while CSK fails to inactivate SFKs whose phospho-tail SH2 docking site is occluded, a state reversed by PTP1B (PMID:9794236, PMID:11329267, PMID:8631775). Substrate recognition combines an active-site mechanism reading the Src tail residues Glu(Y-3)/Gln(Y-1) with a distinct docking site on the catalytic domain (PMID:11329267, PMID:16439366). Catalysis proceeds through a random-order ternary complex requiring two divalent metals, with ADP release rate-limiting under Mn and the chemical step rate-limiting under Mg; the catalytic Asp314 enhances gamma-phosphate electrophilicity and the activation loop acts as an inhibitory element that requires no autophosphorylation (PMID:9425036, PMID:9048573, PMID:7673185, PMID:11551213, PMID:12686554, PMID:10220355). CSK activity is governed by interdomain coupling: its outward-oriented SH2 and SH3 domains brace the active state, the SH3 domain stimulates the catalytic domain via the SH3-SH2 linker, and SH2 engagement of a Cbp/PAG phosphopeptide allosterically orders the active site through cantilever-like motion propagated to the glycine-rich loop (PMID:11884384, PMID:10460171, PMID:11724538, PMID:16002086). Membrane recruitment is the dominant spatial control: CSK is delivered to lipid rafts and cell contacts through SH2-domain binding to the transmembrane adaptor PAG/Cbp and to scaffolds including FAK/paxillin, VE-cadherin pTyr685, integrin alphaIIbbeta3, and FLT3/c-Kit, positioning it adjacent to its SFK substrates (PMID:10790433, PMID:11390365, PMID:7529872, PMID:15861137, PMID:11940607, PMID:23707526). Enzymatic activation is layered onto this localization by PKA phosphorylation at Ser364 (in an SH3-dependent manner) and by Gbetagamma, which both translocate CSK and increase its catalytic activity (PMID:11181701, PMID:12600271, PMID:12062086). Through this regulatory logic CSK sets signaling thresholds in physiological circuits: it enforces receptor-dependent thymocyte developmental checkpoints and tunes the TCR activation threshold and affinity discrimination, restrains BCR/Lyn-Syk signaling, controls platelet integrin-proximal Src, and limits SFK-driven adhesion, migration and proliferation in epithelial and endothelial contexts (PMID:9732874, PMID:26302204, PMID:24317039, PMID:7935444, PMID:29301754, PMID:14712234, PMID:15861137).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1991 High

    Established CSK's core biochemical function — what enzyme controls SFK activity and how — by showing it phosphorylates the SFK C-terminal regulatory tyrosine to repress their activity.

    Evidence in vitro kinase assay with multiple SFK substrates and Lyn Tyr508 mutagenesis

    PMID:1722201

    Open questions at the time
    • Did not resolve how CSK is targeted to SFKs in cells
    • Structural basis of substrate selection unaddressed
  2. 1994 High

    Demonstrated in cells that SFK suppression requires CSK's SH2 and SH3 domains for relocalization to sites of active Src, separating catalytic competence from in-cell regulatory function.

    Evidence Csk mutant rescue in csk-deficient cells with immunofluorescence and loss-of-function in chicken B cells

    PMID:7518562 PMID:7935444

    Open questions at the time
    • Identity of the membrane/scaffold receptors mediating localization not yet defined
    • Did not address downstream signaling consequences quantitatively
  3. 1995 Medium

    Identified scaffold/adaptor partners (paxillin, FAK, GAP-A.p62) that recruit CSK to focal adhesions and cytoskeletal sites, linking CSK localization to adhesion control.

    Evidence co-IP, GST-SH2 pulldown, inducible overexpression and subcellular fractionation

    PMID:7529872 PMID:7544435

    Open questions at the time
    • GAP-A.p62 interaction is single-lab in vitro reconstitution
    • Direct contribution of each scaffold to physiological SFK regulation not dissected
  4. 1998 High

    Resolved the catalytic mechanism and a substrate-state requirement — CSK inactivates only non-autophosphorylated SFKs, and phosphoryl transfer proceeds via a random ternary complex with rate-limiting ADP release (Mn) or chemical step (Mg).

    Evidence in vitro reconstitution with PTP1B rescue, steady-state kinetics, dead-end inhibition and metal substitution

    PMID:9048573 PMID:9425036 PMID:9794236

    Open questions at the time
    • Conformational coupling between active site and regulatory domains not yet visualized
    • Physiological relevance of the autophosphorylation gate in vivo untested
  5. 1999 High

    Provided structural and energetic models of catalysis — kinase-domain crystal structure, the intramolecular SH3-to-catalytic-domain activation, and a two-metal requirement.

    Evidence X-ray crystallography, isolated-domain reconstitution with SPR, metal-substitution kinetics

    PMID:10220355 PMID:10460171 PMID:9878439

    Open questions at the time
    • Full-length conformational regulation not yet captured
    • How extracellular signals modulate domain coupling unknown
  6. 2001 High

    Defined the allosteric regulatory architecture — full-length structure showing SH2-kinase coupling, NMR mapping of the SH3/linker activation surface, and substrate determinants in the Src tail.

    Evidence full-length crystallography, NMR chemical-shift mapping with mutagenesis, alanine scanning of Src tail

    PMID:11329267 PMID:11724538 PMID:11884384

    Open questions at the time
    • Dynamic coupling of SH2 engagement to active-site ordering not yet measured
    • Role of Src oligomerization in cells unverified
  7. 2001 High

    Established the membrane-recruitment and PKA-activation paradigm placing CSK in lipid rafts as a tonic inhibitor of TCR signaling, controlled by PAG/Cbp binding and Ser364 phosphorylation.

    Evidence co-IP, raft fractionation, dominant-negative displacement, in vitro PKA phosphorylation with functional IL-2/NFAT readouts; pre-steady-state kinetics

    PMID:10790433 PMID:11158295 PMID:11181701 PMID:11390365 PMID:11551213

    Open questions at the time
    • Quantitative contribution of localization vs. enzymatic activation not separated until later
    • Whether PAG is the sole raft anchor unresolved
  8. 2002 High

    Showed CSK activation is multi-input — Gbetagamma both translocates and activates CSK to drive actin stress fibers, and nucleotide-induced conformational changes propagate from active site to regulatory domains.

    Evidence Csk-deficient MEF rescue with catalytic mutant, Gbetagamma interaction/activation assay, DXMS with nucleotide analogs, platelet co-IP

    PMID:11940607 PMID:12062086 PMID:12417200

    Open questions at the time
    • Structural detail of the Gbetagamma-CSK interface absent
    • Mechanism linking CSK to actin remodeling downstream of SFKs incompletely defined
  9. 2003 High

    Integrated spatial and enzymatic PKA control and defined the activation loop as an inhibitory element, refining how CSK activity is tuned.

    Evidence raft fractionation with FRET kinase assay, SPR of SH3-dependent PKA activation, activation-loop mutagenesis with thrombin-cleavage rescue

    PMID:12600271 PMID:12665526 PMID:12686554

    Open questions at the time
    • In vivo stoichiometry of PKA-Ser364 phosphorylation unknown
    • Physiological signals that relieve activation-loop inhibition unclear
  10. 2004 High

    Placed CSK within phosphatase-coordinated SFK control circuits and SFK-dependent epithelial phenotypes, defining upstream regulators (Shp2, PTP-HSCF) and adhesion/transport outputs.

    Evidence Shp2-deficient cell epistasis, colon-cancer overexpression/dominant-negative phenotypes, Csk overexpression in OKP cells

    PMID:14712234 PMID:14967142 PMID:7541536

    Open questions at the time
    • Colon cancer and NHE-3 phenotypes are single-lab
    • Direct vs. indirect contribution of CSK to invasion not fully separated
  11. 2005 High

    Demonstrated allosteric activation by SH2-ligand binding and identified VE-cadherin pTyr685 as a junctional CSK anchor coupling cell density to growth control.

    Evidence rapid quench flow with Cbp peptide, DXMS, normal mode analysis; reciprocal co-IP, GST-SH2 pulldown, RNAi and Y685F rescue

    PMID:15861137 PMID:16002086

    Open questions at the time
    • In-cell allosteric activation by endogenous PAG not directly measured
    • How density signals control VE-cadherin Tyr685 phosphorylation unclear
  12. 2006 High

    Defined a docking-based substrate-recognition mechanism on the CSK catalytic domain and dissected Cbp-mediated dual control of Lyn in cytokine signaling.

    Evidence mutagenesis of CSK docking site and Src/Yes docking determinants with kinetics; Cbp Tyr314 mutagenesis with ubiquitination assays

    PMID:16439366 PMID:16920712

    Open questions at the time
    • Generality of docking-based recognition across all SFKs untested
    • Temporal handoff from CSK to SOCS1 mechanism incompletely defined
  13. 2013 High

    Using analog-sensitive CSK in vivo, established CSK as the gatekeeper of receptor-dependent developmental checkpoints and revealed an actin-remodeling step downstream of SFK activation.

    Evidence conditional Csk knockout in thymocytes; analog-sensitive Csk knockin with cytoskeletal perturbation; FLT3/c-Kit co-IP and knockdown

    PMID:23707526 PMID:24317039 PMID:9732874

    Open questions at the time
    • Mechanism by which actin remodeling licenses downstream TCR signaling unresolved
    • FLT3/c-Kit regulation is single-lab Medium-confidence
  14. 2015 High

    Quantified CSK as the principal determinant of TCR signaling threshold and ligand affinity discrimination by titrating chemical-genetic inhibition.

    Evidence analog-sensitive Csk knockin mice with graded inhibitor dosing and functional/biochemical readouts

    PMID:26302204

    Open questions at the time
    • Molecular basis of threshold setting not reduced to specific phosphorylation kinetics
    • Whether the same logic operates in other receptor systems untested here
  15. 2018 High

    Mapped cooperative inhibitory circuits and negative feedback by combining CSK loss with other regulators (PAG/PTPN22/Dok adaptors; CD148 in platelets; LYP dissociation).

    Evidence PAG-knockout and double-knockout epistasis, conditional Csk/CD148 double-KO platelets, LYP chemical probe with imaging and co-IP

    PMID:22426112 PMID:27926878 PMID:29301754

    Open questions at the time
    • Quantitative hierarchy among redundant CSK adaptors unresolved
    • Feedback receptor-downregulation mechanism in platelets only partially defined
  16. 2023 Medium

    Extended CSK's negative-regulatory role to additional scaffolds and physiological barriers — connexin43/PTEN ternary complexes, Thy-1/CBP integrin signaling, ZO tight-junction scaffolds, P2X3 receptor inhibition, and Adipsin-driven endothelial barrier protection.

    Evidence co-IP, domain pulldowns, RNAi and phospho-readouts across multiple cell systems; in vitro kinase assay and electrophysiology for P2X3

    PMID:18086565 PMID:19509283 PMID:27391443 PMID:27842221 PMID:37237266

    Open questions at the time
    • Most of these scaffold/substrate links are single-lab
    • Direct vs. SFK-mediated contributions not always separated

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the distinct activation inputs (PAG/Cbp SH2 engagement, PKA-Ser364, Gbetagamma, scaffold recruitment) are integrated quantitatively in a living cell to set net CSK activity, and how CSK partner choice is selected among redundant adaptors, remain unresolved.
  • No unified model integrating spatial and enzymatic activation in vivo
  • Determinants of adaptor selection among PAG/PTPN22/Dok/VE-cadherin/integrin scaffolds unknown
  • Structure of full-length CSK engaged with a membrane adaptor on substrate unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 5 GO:0016740 transferase activity 4 GO:0098772 molecular function regulator activity 3 GO:0140657 ATP-dependent activity 3
Localization
GO:0005886 plasma membrane 5 GO:0005856 cytoskeleton 3 GO:0005829 cytosol 2
Pathway
R-HSA-168256 Immune System 5 R-HSA-162582 Signal Transduction 4 R-HSA-1500931 Cell-Cell communication 3 R-HSA-109582 Hemostasis 2 R-HSA-1266738 Developmental Biology 1
Partners
FAKITGA2B/INTEGRIN ALPHAIIBBETA3LCKPAG/CBPPAXILLINPTP-HSCFPTPN22/LYPVE-CADHERIN
Complex memberships
Cx43/PTEN/Csk/c-Src complexThy-1/CBP/Csk complex

Evidence

Reading pass · 46 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1991 CSK specifically phosphorylates the negative regulatory C-terminal tyrosine of Src family kinases (p60c-src, p56lyn, p59fyn), and this phosphorylation represses their kinase activities. Tyrosine 508 of p56lyn was identified as essential for this phosphorylation. In vitro kinase assay, site-directed mutagenesis, Western blot The Journal of biological chemistry High 1722201
1999 Crystal structure of the CSK kinase domain co-complexed with staurosporine resolved at 2.4 Å. The structure revealed the ATP-binding cleft between N- and C-terminal lobes, conserved Lys328 and Glu267 forming a molecular pivot for lobe movement, and unique orientations of Asp332 and Phe333 suggesting inhibitor binding via induced fit. X-ray crystallography (molecular replacement) Journal of molecular biology High 9878439
2002 Full-length crystal structure of Csk revealed that SH2 and SH3 domains are oriented outward (distinct from inactive SFKs) with binding pockets accessible for intermolecular interaction. In active conformations, the SH2-kinase linker stabilizes the active state through direct SH2-kinase domain linkage; SH2 domain rotation destroys this linkage in inactive conformations, suggesting Csk is regulated through SH2-kinase domain coupling. X-ray crystallography (full-length protein) The Journal of biological chemistry High 11884384
1994 Csk suppression of Src requires functional SH2, SH3, and catalytic domains. An SH3 deletion mutant retained in vitro kinase activity but failed to suppress Src in cells. When Src is active, Csk relocalizes from cytosol to podosomes via its SH3 and SH2 domains; SH3 or SH2 domain mutants do not relocalize, explaining their failure to regulate Src. Expression of Csk mutants in csk-deficient cells, immunofluorescence localization, in vitro kinase assay Molecular and cellular biology High 7518562
1995 Overexpressed Csk localizes to focal adhesions via its SH2 and SH3 domains (not catalytic activity). Csk forms a complex with paxillin in cells and its SH2 domain interacts with FAK and paxillin in vitro. Catalytically active Csk overexpression causes cell rounding, loss of adhesion, and redistribution of αvβ5 integrin; catalytically inactive mutant does not produce these effects. Inducible overexpression, immunofluorescence, co-immunoprecipitation, in vitro binding (SH2 domain GST pulldown), point and deletion mutagenesis Molecular and cellular biology High 7529872
1998 Csk phosphorylates and inactivates Src only when Src is not previously autophosphorylated at its activation loop tyrosine. Autophosphorylated Src can still be phosphorylated by Csk at the C-terminal tail but is not inactivated, because the SH2 binding site for phospho-Tyr is inaccessible. PTP1B dephosphorylation of the Src autophosphorylation site restores Csk-mediated inactivation. In vitro kinase assay, pre-incubation with ATP-Mg, site-directed mutagenesis (Yes Y-to-F mutant), PTP1B dephosphorylation rescue Oncogene High 9794236
1998 CSK catalyzes phosphoryl transfer via a ternary complex random-substrate-binding mechanism. ADP release is rate-limiting with Mn as cofactor; the chemical (phosphoryl transfer) step is fully rate-determining with Mg. Asp314 enhances gamma-phosphate reactivity toward electrophilic attack (thio-effect analysis with D314E mutant). Steady-state kinetics, dead-end inhibitor analysis, viscosity experiments, thio effects with wild-type and D314E mutant Csk Biochemistry High 9048573 9425036
1995 The catalytic base Asp314 of Csk is not required for early tyrosine deprotonation (trifluorotyrosine substrate is phosphorylated with similar efficiency). D314E mutation reduces kcat ~10,000-fold with minimal effect on substrate Km, and thio-effect analysis suggests Asp314 enhances gamma-phosphate electrophilicity. In vitro kinase assay with unnatural amino acid substrate, site-directed mutagenesis (D314E), thio-effect measurements The Journal of biological chemistry High 7673185
1999 The Csk SH3 domain intramolecularly interacts with the catalytic domain to stimulate kinase activity (~100-fold reduction when catalytic domain alone is expressed). The interaction surface on SH3 involves the SH3-SH2 linker region, distinct from the classical type-II polyproline helix-binding surface. Expression of isolated Csk domains in E. coli, in vitro kinase assay, trans-stimulation, surface plasmon resonance, site-directed mutagenesis Biochemistry High 10460171
2001 Pre-steady-state kinetic analysis shows CSK phosphoryl transfer to peptide substrate is fast (k3 ≥ 140 s⁻¹) and favorable, with rate-limiting ADP release (koff ~0.6 s⁻¹ ≈ kcat). Viscosometric studies indicate slow conformational changes are coupled to ADP dissociation. Rapid quench flow, stopped-flow fluorescence, viscosometric experiments Biochemistry High 11551213
2001 The SH3 and SH2 domains of Csk's substrate Src are dispensable for efficient Csk-catalyzed phosphorylation; the catalytic domain and tail of Src are sufficient. Key Src tail residues Glu (Y-3) and Gln (Y-1) are critical determinants of substrate efficiency for Csk. Src dimerization/oligomerization appears important for high-efficiency Csk phosphorylation. In vitro kinase assay with purified recombinant proteins and alanine-scanning mutants of Src tail Biochemistry High 11329267
2001 Csk physically interacts with PTP-HSCF (third member of PEP phosphatase family) via the Csk SH2 domain binding to tyrosine-phosphorylated sites in PTP-HSCF's non-catalytic region. Csk and PTP-HSCF synergize to inhibit Src family kinases; this cooperativity depends on the domains mediating their interaction. PTP-HSCF selectively dephosphorylates the positive regulatory tyrosine of Src-related kinases. Yeast two-hybrid, co-immunoprecipitation in mammalian cells and hematopoietic cells, transfection assays Molecular and cellular biology High 11158295
2000 PAG (phosphoprotein associated with GEMs/Cbp) is a transmembrane adaptor that constitutively binds Csk via its phosphorylated cytoplasmic tyrosines in resting T cells. After T cell activation, PAG is dephosphorylated and dissociates from Csk. PAG expression in COS cells recruits endogenous Csk and alters Src kinase activity. Overexpression in Jurkat cells downregulates TCR-mediated NFAT activation. Co-immunoprecipitation, mass spectrometry identification, COS cell transfection, Jurkat overexpression with reporter assay The Journal of experimental medicine High 10790433
2001 PKA phosphorylates Csk at Ser364 in vitro and in vivo, leading to a 2-4-fold increase in Csk kinase activity. This PKA-mediated Csk activation is necessary for cAMP-mediated inhibition of TCR signaling and IL-2 secretion. Both PKA type I and Csk are targeted to lipid rafts where Lck phosphorylation by activated Csk is enhanced. In vitro PKA phosphorylation of Csk, kinase activity assay, lipid raft fractionation, IL-2 secretion assay, phosphorylation site mutants The Journal of experimental medicine High 11181701
2001 Csk is constitutively present in lipid rafts through interaction with PAG/Cbp. Upon TCR triggering, PAG/Cbp is dephosphorylated leading to Csk dissociation from rafts. A dominant-negative Csk that displaces endogenous Csk from lipid rafts results in elevated basal TCR-zeta phosphorylation and enhanced TCR responses, establishing that raft-localized Csk tonically inhibits T cell activation. Lipid raft fractionation, dominant-negative Csk expression, TCR-zeta phosphorylation assay, NFAT-AP1 reporter assay The Journal of biological chemistry High 11390365
2003 PKA regulates Csk by two mechanisms: (1) increasing Cbp/PAG phosphorylation to augment Csk recruitment to lipid rafts, reducing TCR-induced Csk dissociation; and (2) directly increasing Csk phosphotransferase activity. cAMP-mediated inhibition of TCR signaling requires raft-associated Csk, as displacing Csk from rafts abolishes PGE2-mediated inhibition. Raft fractionation, co-immunoprecipitation, FRET-based kinase activity assay, NFAT-AP1 reporter The Journal of biological chemistry High 12665526
2002 Csk is required for G protein (Gβγ, Gα12, Gα13, Gαq)-induced actin stress fiber formation. In Csk-deficient MEFs, GPCR-induced actin reorganization is completely blocked and reintroduction of Csk restores it. Csk catalytic activity is required; Gβγ both translocates Csk to the plasma membrane and directly increases Csk kinase activity. Csk-deficient MEFs, Csk reintroduction, catalytic mutant rescue, biochemical Gβγ-Csk interaction and kinase activation assay Developmental cell High 12062086
2002 DXMS analysis of CSK shows that ATP-analog AMPPNP and product ADP protect overlapping but distinct regions including the active site, activation loop, helix G, SH2 domain, and SH2-kinase linker, demonstrating that phosphoryl transfer induces unique conformational changes propagated from active site to regulatory domains. Hydrogen-deuterium exchange mass spectrometry (DXMS) with nucleotide analogs Journal of molecular biology High 12417200
2004 Shp2 promotes Src family kinase activation by dephosphorylating PAG/Cbp, thereby reducing Csk recruitment to SFKs. In Shp2-deficient cells, SFK inhibitory C-terminal tyrosines are hyperphosphorylated. This places Shp2 upstream of Csk in controlling SFK activity and downstream signaling (Plcγ1, Ras/Erk). Shp2-deficient cells, phosphorylation analysis of SFK regulatory tyrosines, Plcγ1 phosphorylation assay Molecular cell High 14967142
2002 Csk is constitutively associated with integrin αIIbβ3 in platelets. Upon fibrinogen binding, Csk dissociates from αIIbβ3 concomitant with Src Tyr-529 dephosphorylation and Src Tyr-418 phosphorylation (activation), placing Csk as a direct negative regulator of integrin-proximal Src in platelet spreading. Co-immunoprecipitation from platelets, phospho-specific antibodies, integrin engagement assay The Journal of cell biology High 11940607
2005 Csk binds via its SH2 domain to phosphorylated Tyr685 of VE-cadherin. VE-cadherin recruits Csk to cell contacts; this interaction increases with cell density. VE-cadherin-Y685F mutant abolishes Csk binding and confers higher growth density. Csk overexpression inhibits endothelial cell proliferation in a VE-cadherin phospho-Y685-dependent manner; Csk RNAi enhances proliferation. Co-immunoprecipitation, GST-SH2 pulldown, inducible Csk overexpression, RNAi knockdown, proliferation assay with Y685F mutant The EMBO journal High 15861137
2005 Binding of a Cbp-derived phosphopeptide to the Csk SH2 domain enhances Src recognition (lowers Km) by increasing phosphoryl transfer rate, detected by rapid quench flow. DXMS shows the Cbp peptide induces conformational changes propagating from the SH2 domain through the SH2-kinase linker to the glycine-rich loop of the active site, suggesting cantilever-like SH2 motion orders the active site. Rapid quench flow kinetics, DXMS, computational normal mode analysis Journal of molecular biology High 16002086
2001 NMR chemical shift mapping shows the Csk SH3 domain binds the catalytic domain at the SH3-SH2 linker region and N-terminal tail (not the classical polyproline-binding RT-loop surface). Site-directed mutagenesis of the SH3-SH2 linker reduces Csk kinase activity up to 5-fold, confirming this intradomain interaction activates the catalytic domain. NMR chemical shift perturbation mapping, site-directed mutagenesis, in vitro kinase assay Journal of molecular biology High 11724538
2003 PKA-mediated activation of Csk by Ser364 phosphorylation depends on the intact SH3 domain. Isolated Csk kinase domain is phosphorylated by PKA at S364 but is not significantly activated unless the SH3 domain is present. PKA phosphorylation facilitates the SH3-kinase domain interaction, measured by surface plasmon resonance. In vitro PKA phosphorylation of Csk domains, kinase activity assay, surface plasmon resonance The Biochemical journal High 12600271
2006 Csk recognizes Src family kinase substrates through a docking site on its catalytic domain that is distinct from the active site. Docking determinants on Src recognized by this site were identified; similar docking-based recognition was confirmed for Yes. This establishes a docking-based substrate recognition mechanism for Csk. In vitro binding assays, mutagenesis of Csk docking site and Src docking determinants, kinase assay The Journal of biological chemistry High 16439366
2003 Csk activation loop lacks tyrosine residues, and specific residues in this loop have little function in Src phosphorylation. Thrombin-cleavage of the activation loop restores full activity in loop-insertion mutants that are nearly inactive toward artificial substrates, indicating the activation loop acts as an inhibitory regulatory structure and is dispensable for catalysis when removed. Extensive site-directed mutagenesis, loop replacement, engineered thrombin cleavage site, kinase assay with physiological (Src) and artificial substrates The Journal of biological chemistry High 12686554
1994 Csk-negative chicken B cells have constitutively active Lyn (hyperphosphorylated at autophosphorylation site) and constitutively activated Syk, demonstrating Csk maintains Lyn and downstream Syk in inactive states. BCR crosslinking was still required for full downstream signaling (Ca2+ mobilization, IP3 generation) despite constitutive kinase activation. Csk-deficient B cell clones (gene disruption), kinase activity assay, phosphorylation analysis, calcium flux, IP3 measurement Molecular and cellular biology High 7935444
1998 T cell development is controlled by Csk: conditional inactivation of Csk in immature thymocytes abrogates the requirement for preTCR, αβTCR, and MHC class II for development of DP and CD4+ SP thymocytes, placing Csk as the gatekeeper that enforces receptor-dependent developmental checkpoints by restraining Src-family kinases. Conditional Csk gene knockout in thymocytes (Cre-lox), flow cytometric analysis of thymic development Nature High 9732874
2013 Inhibition of an analog-sensitive Csk variant (CskAS) in thymocytes induces potent SFK activation and proximal TCR signaling up to PLCγ1 phosphorylation, but downstream signals (IP3, Ca2+, Erk phosphorylation) are impaired. Actin cytoskeleton remodeling (pharmacological or via CD28 costimulation) rescues these downstream defects, revealing that Csk controls a checkpoint requiring actin remodeling for full TCR signaling. Analog-sensitive Csk knockin mice, chemical-genetic inhibition, phosphorylation analysis, IP3/Ca2+ measurement, cytoskeletal perturbation Nature immunology High 24317039
1995 CSK directly associates with the GTPase-activating protein-associated p62 (GAP-A.p62) protein via the CSK SH2 domain (reconstituted in vitro with GST-CSK and GST-SH2 domain fusions). This complex localizes to membrane/cytoskeletal fractions in v-Src NIH 3T3 cells, suggesting GAP-A.p62 as a docking protein mediating CSK translocation to sites of Src activity. Co-immunoprecipitation, GST pulldown in vitro reconstitution, subcellular fractionation Molecular and cellular biology Medium 7544435
1996 Csk interacts with phosphorylated Lck via the Csk SH2 domain; this interaction requires Lck autophosphorylation at Tyr394 (activation loop). Autophosphorylated Lck is preferentially phosphorylated by Csk at its negative regulatory Tyr505, suggesting activated Src-family kinases are preferential Csk substrates. BIAcore (SPR) real-time binding assay, yeast two-hybrid, in vitro kinase assay with site-directed Lck mutants The Journal of biological chemistry High 8631775
2004 Csk overexpression in colon cancer cells decreases SFK activation, increases E-cadherin-mediated cell-cell contacts, decreases focal contacts, and reduces cell adhesion/migration/invasiveness. Dominant-negative Csk produces opposite effects: elevated SFK/FAK/paxillin phosphorylation, cell scattering, increased focal contacts and invasiveness. All these events are integrin-dependent. Stable overexpression and dominant-negative expression, kinase assay, cell adhesion/migration/invasion assay, phospho-FAK/paxillin immunoblot Oncogene Medium 14712234
2007 p140Cap adaptor protein binds Src and activates Csk, leading to Src inhibition. p140Cap silencing increases cell spreading, migration, and Src activity; increased p140Cap expression activates Csk and inhibits Src and downstream signaling, cell motility, and invasion. RNAi knockdown, co-immunoprecipitation, kinase activity assay, cell migration/invasion assay The EMBO journal Medium 17525734
2009 Csk directly phosphorylates Tyr393 of the P2X3 receptor in vitro (in vitro kinase assay in HEK cells), strongly inhibiting receptor currents. Csk knockdown in HEK and trigeminal neurons potentiates P2X3 responses, confirming constitutive Csk-mediated inhibition of P2X3. NGF levels regulate Csk activity in sensory neurons to control P2X3 sensitization. In vitro kinase assay, site-directed mutagenesis (structural modeling-guided), RNAi knockdown, electrophysiology The Journal of biological chemistry High 19509283
2012 LYP (lymphoid tyrosine phosphatase) inhibits T cell activation when dissociated from CSK. Dissociation of the LYP-CSK complex is necessary for LYP recruitment to the plasma membrane where it downmodulates TCR signaling. The autoimmunity-associated LYP variant that cannot bind CSK shows reduced TCR-mediated signaling. Spatiotemporal dynamics imaging, selective LYP chemical probe, co-immunoprecipitation, functional T cell activation assays Nature chemical biology High 22426112
2016 PAG (Cbp) genetically cooperates with PTPN22 and Dok adaptors to inhibit effector T cell activation. In PAG-deficient mice, Csk associates more with PTPN22 and Dok adaptors as alternative partners. Combining PAG deficiency with PTPN22 or Dok deficiency further enhances effector T cell responses, establishing a cooperative inhibitory circuit. PAG-knockout mice, double-knockout genetic epistasis, co-immunoprecipitation, T cell activation assays Cell reports High 27926878
2016 Connexin43 (Cx43) recruits both PTEN and Csk to the region between residues 266-283 of its C-terminus, forming a ternary complex with c-Src. Pulldown assays showed this Cx43 region is sufficient to recruit c-Src, PTEN, and Csk and to inhibit oncogenic c-Src activity. Csk and PTEN silencing reduces the antiproliferative effect of Cx43. Confocal microscopy, co-immunoprecipitation, GST pulldown (Cx43 domain fragments), RNAi knockdown, proliferation assay Oncotarget Medium 27391443
2016 Upon αvβ3 integrin engagement of Thy-1, Csk is present in the Thy-1/CBP/Csk complex at the plasma membrane; integrin binding causes Src inactivation and exclusion from this complex. CBP silencing abolishes Csk recruitment and the downstream RhoA/ROCK neurite retraction signaling, establishing CBP as the key transducer linking Thy-1 to Csk-mediated Src inactivation. Single-molecule tracking, nanoscopy, co-immunoprecipitation, RNAi knockdown, RhoA activation assay Biochimica et biophysica acta. Molecular cell research Medium 27842221
2018 Simultaneous ablation of Csk and CD148 in platelets causes dramatic SFK hyperactivation, demonstrating these proteins are essential regulators of platelet SFK activity. Paradoxically, this leads to reduced thrombosis due to downregulation of GPVI-FcRγ and CLEC-2 ITAM receptors and upregulation of inhibitory G6b-B/Shp1/Shp2 signaling as a negative feedback. Conditional Csk/CD148 double-knockout mice, analog-sensitive Csk model, platelet SFK activity assay, receptor expression analysis, bleeding/thrombosis models Blood High 29301754
2006 Cbp/PAG phosphorylation by Lyn recruits Csk (and Ctk) to suppress Lyn kinase activity within minutes of Epo stimulation. A single phosphotyrosine (Tyr314) on Cbp serves dual function: recruiting Csk/Ctk for rapid Lyn suppression and later recruiting SOCS1 for Lyn ubiquitination and degradation. Co-immunoprecipitation, in vitro kinase assay, mutagenesis of Cbp Tyr314, ubiquitination assay in Epo-responsive cells The Journal of biological chemistry High 16920712
2013 CSK interacts with FLT3 and c-Kit receptor tyrosine kinases in a phosphorylation-dependent manner via its SH2 domain; CSK is recruited from cytoplasm to the inner cell membrane upon ligand stimulation. CSK knockdown or inhibition increases FLT3- and c-Kit-mediated Akt and Erk phosphorylation and downstream signaling, demonstrating CSK negatively regulates type III RTK signaling. Co-immunoprecipitation, SH2-domain binding assays, siRNA knockdown, phosphorylation analysis, subcellular fractionation Cellular signalling Medium 23707526
2007 ZO-1 and ZO-2 (tight junction proteins) serve as Csk-binding proteins (identified by tandem affinity purification/LC-MS/MS). ZO-2 is phosphorylated upon Src transformation and binds Csk in a Csk SH2-dependent manner, establishing ZO proteins as novel Src/Csk scaffolds at cell junctions. Tandem affinity purification, LC-MS/MS proteomics, co-immunoprecipitation, Csk SH2 domain binding assay Biochemical and biophysical research communications Medium 18086565
2004 Csk overexpression in HeLa cells reduces acid-induced c-Src activation and blocks acid-induced NHE-3 mRNA upregulation and Na+/H+ antiporter activity, placing Src-family kinases downstream of acid sensing as required for NHE-3 regulation. Stable Csk overexpression in OKP cells, Src kinase activity assay, NHE-3 mRNA and transporter activity measurement Proceedings of the National Academy of Sciences Medium 7541536
2015 Inhibition of CskAS during TCR stimulation leads to stronger, more prolonged TCR signaling and increased T cell proliferation. Even a small increase in SFK activity (via partial Csk inhibition) is sufficient to potentiate T cell responses to weak agonists, establishing Csk as the key determinant of TCR signaling threshold and affinity discrimination. Analog-sensitive Csk knockin mice, dose-titrated chemical inhibitor, T cell activation and proliferation assays, signaling phosphorylation analysis eLife High 26302204
2023 Adipsin acts upstream of Csk in cardiac microvascular endothelial cells. LC-MS/MS and co-IP identified Csk as a direct downstream regulator of Adipsin. Csk knockdown increases Src phosphorylation (Tyr416) and VE-cadherin phosphorylation (Tyr685, Tyr731) and abolishes Adipsin-induced inhibition of VE-cadherin internalization and protection of endothelial barrier integrity. LC-MS/MS proteomics, co-immunoprecipitation, siRNA knockdown, phospho-specific immunoblot, permeability assay BMC medicine Medium 37237266
1999 Csk requires two divalent metal cations for activity: one to form the ATP-Mg complex and a second free Mg2+ for activation. The second site can be occupied by Mn2+, Co2+, Ni2+, or Zn2+ with much higher affinity than Mg2+. Zn2+ acts as a dead-end inhibitor at this site competitive against free Mg2+. Metal identity at this site influences substrate affinity. Steady-state kinetics with divalent metal substitution, inhibition analysis Biochemistry High 10220355

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1991 CSK: a protein-tyrosine kinase involved in regulation of src family kinases. The Journal of biological chemistry 472 1722201
2000 Phosphoprotein associated with glycosphingolipid-enriched microdomains (PAG), a novel ubiquitously expressed transmembrane adaptor protein, binds the protein tyrosine kinase csk and is involved in regulation of T cell activation. The Journal of experimental medicine 383 10790433
2004 Shp2 regulates SRC family kinase activity and Ras/Erk activation by controlling Csk recruitment. Molecular cell 377 14967142
2002 Coordinate interactions of Csk, Src, and Syk kinases with [alpha]IIb[beta]3 initiate integrin signaling to the cytoskeleton. The Journal of cell biology 347 11940607
2001 Activation of the COOH-terminal Src kinase (Csk) by cAMP-dependent protein kinase inhibits signaling through the T cell receptor. The Journal of experimental medicine 270 11181701
2012 Regulation of the SRC family kinases by Csk. International journal of biological sciences 247 23139636
2006 PRL3 promotes cell invasion and proliferation by down-regulation of Csk leading to Src activation. The Journal of biological chemistry 141 17192274
1999 Structure of the protein tyrosine kinase domain of C-terminal Src kinase (CSK) in complex with staurosporine. Journal of molecular biology 130 9878439
2002 Structure of the carboxyl-terminal Src kinase, Csk. The Journal of biological chemistry 127 11884384
1994 Csk suppression of Src involves movement of Csk to sites of Src activity. Molecular and cellular biology 127 7518562
2001 Release from tonic inhibition of T cell activation through transient displacement of C-terminal Src kinase (Csk) from lipid rafts. The Journal of biological chemistry 125 11390365
1998 Csk controls antigen receptor-mediated development and selection of T-lineage cells. Nature 119 9732874
2012 LYP inhibits T-cell activation when dissociated from CSK. Nature chemical biology 117 22426112
1995 Overexpressed Csk tyrosine kinase is localized in focal adhesions, causes reorganization of alpha v beta 5 integrin, and interferes with HeLa cell spreading. Molecular and cellular biology 117 7529872
1994 Ctk: a protein-tyrosine kinase related to Csk that defines an enzyme family. Proceedings of the National Academy of Sciences of the United States of America 114 7511815
2005 Association of Csk to VE-cadherin and inhibition of cell proliferation. The EMBO journal 103 15861137
1999 Suppression of arthritic bone destruction by adenovirus-mediated csk gene transfer to synoviocytes and osteoclasts. The Journal of clinical investigation 95 10411542
2012 CSK regulatory polymorphism is associated with systemic lupus erythematosus and influences B-cell signaling and activation. Nature genetics 92 23042117
1998 Regulation of mouse PECAM-1 tyrosine phosphorylation by the Src and Csk families of protein-tyrosine kinases. The Journal of biological chemistry 91 9624175
2005 C-terminal Src kinase (CSK) and CSK-homologous kinase (CHK)--endogenous negative regulators of Src-family protein kinases. Growth factors (Chur, Switzerland) 85 16243715
1998 Autophosphorylation of Src and Yes blocks their inactivation by Csk phosphorylation. Oncogene 82 9794236
1994 Functional analysis of Csk in signal transduction through the B-cell antigen receptor. Molecular and cellular biology 80 7935444
2013 Inhibition of the kinase Csk in thymocytes reveals a requirement for actin remodeling in the initiation of full TCR signaling. Nature immunology 79 24317039
2010 CD45-Csk phosphatase-kinase titration uncouples basal and inducible T cell receptor signaling during thymic development. Immunity 79 20346773
1998 Peptide and protein phosphorylation by protein tyrosine kinase Csk: insights into specificity and mechanism. Biochemistry 79 9425036
2003 Protein tyrosine kinases Src and Csk: a tail's tale. Current opinion in chemical biology 78 14580561
2007 p140Cap protein suppresses tumour cell properties, regulating Csk and Src kinase activity. The EMBO journal 75 17525734
1993 Functional and physical interaction of protein-tyrosine kinases Fyn and Csk in the T-cell signaling system. The Journal of biological chemistry 75 8262983
1999 Reduced C-terminal Src kinase (Csk) activities in hepatocellular carcinoma. Hepatology (Baltimore, Md.) 72 9918913
1995 The nonreceptor protein-tyrosine kinase CSK complexes directly with the GTPase-activating protein-associated p62 protein in cells expressing v-Src or activated c-Src. Molecular and cellular biology 72 7544435
2002 Csk, a critical link of g protein signals to actin cytoskeletal reorganization. Developmental cell 70 12062086
1994 Ntk: a Csk-related protein-tyrosine kinase expressed in brain and T lymphocytes. Proceedings of the National Academy of Sciences of the United States of America 69 8197166
2002 Phosphorylation driven motions in the COOH-terminal Src kinase, CSK, revealed through enhanced hydrogen-deuterium exchange and mass spectrometry (DXMS). Journal of molecular biology 68 12417200
1997 Translocation of the Csk homologous kinase (Chk/Hyl) controls activity of CD36-anchored Lyn tyrosine kinase in thrombin-stimulated platelets. The EMBO journal 68 9171348
2013 Fulvestrant-induced cell death and proteasomal degradation of estrogen receptor α protein in MCF-7 cells require the CSK c-Src tyrosine kinase. PloS one 66 23593342
2004 Oxidative stress activates both Src-kinases and their negative regulator Csk and induces phosphorylation of two targeting proteins for Csk: caveolin-1 and paxillin. Experimental cell research 66 14980511
2005 The ubiquitously expressed Csk adaptor protein Cbp is dispensable for embryogenesis and T-cell development and function. Molecular and cellular biology 65 16287865
2005 Cbp deficiency alters Csk localization in lipid rafts but does not affect T-cell development. Molecular and cellular biology 63 16166631
1999 Domain interactions in protein tyrosine kinase Csk. Biochemistry 61 10460171
1997 Divalent ion effects and insights into the catalytic mechanism of protein tyrosine kinase Csk. Biochemistry 60 9048573
2007 CSK controls retinoic acid receptor (RAR) signaling: a RAR-c-SRC signaling axis is required for neuritogenic differentiation. Molecular and cellular biology 56 17325034
2003 Combined spatial and enzymatic regulation of Csk by cAMP and protein kinase a inhibits T cell receptor signaling. The Journal of biological chemistry 55 12665526
2004 Drosophila Src-family kinases function with Csk to regulate cell proliferation and apoptosis. Oncogene 53 15107833
2001 Molecular determinants for Csk-catalyzed tyrosine phosphorylation of the Src tail. Biochemistry 53 11329267
1995 The role of the catalytic base in the protein tyrosine kinase Csk. The Journal of biological chemistry 53 7673185
2016 Connexin43 recruits PTEN and Csk to inhibit c-Src activity in glioma cells and astrocytes. Oncotarget 52 27391443
2005 Coupled motions in the SH2 and kinase domains of Csk control Src phosphorylation. Journal of molecular biology 52 16002086
1996 Csk enhances insulin-stimulated dephosphorylation of focal adhesion proteins. Molecular and cellular biology 52 8756634
1995 Overexpression of csk inhibits acid-induced activation of NHE-3. Proceedings of the National Academy of Sciences of the United States of America 52 7541536
2001 SH2 domain-mediated interaction of inhibitory protein tyrosine kinase Csk with protein tyrosine phosphatase-HSCF. Molecular and cellular biology 51 11158295
1995 The Src and Csk families of tyrosine protein kinases in hemopoietic cells. Seminars in immunology 50 8520026
2016 Astrocyte-to-neuron communication through integrin-engaged Thy-1/CBP/Csk/Src complex triggers neurite retraction via the RhoA/ROCK pathway. Biochimica et biophysica acta. Molecular cell research 46 27842221
1999 The Csk homologous kinase associates with TrkA receptors and is involved in neurite outgrowth of PC12 cells. The Journal of biological chemistry 46 10329710
2014 Trastuzumab-induced recruitment of Csk-homologous kinase (CHK) to ErbB2 receptor is associated with ErbB2-Y1248 phosphorylation and ErbB2 degradation to mediate cell growth inhibition. Cancer biology & therapy 45 24835103
2001 Functional analysis of Csk and CHK kinases in breast cancer cells. The Journal of biological chemistry 44 11445575
1999 Substitution studies of the second divalent metal cation requirement of protein tyrosine kinase CSK. Biochemistry 44 10220355
2000 Overexpression of the csk gene suppresses tumor metastasis in vivo. International journal of cancer 43 11054667
1997 Chk, a Csk family tyrosine protein kinase, exhibits Csk-like activity in fibroblasts, but not in an antigen-specific T-cell line. The Journal of biological chemistry 42 8995444
2015 Small molecule inhibition of Csk alters affinity recognition by T cells. eLife 41 26302204
2006 Csk-binding protein mediates sequential enzymatic down-regulation and degradation of Lyn in erythropoietin-stimulated cells. The Journal of biological chemistry 41 16920712
1994 Identification and characterization of Batk, a predominantly brain-specific non-receptor protein tyrosine kinase related to Csk. Journal of neuroscience research 41 7807586
2004 Csk defines the ability of integrin-mediated cell adhesion and migration in human colon cancer cells: implication for a potential role in cancer metastasis. Oncogene 38 14712234
1995 Structural requirements for the efficient regulation of the Src protein tyrosine kinase by Csk. Oncogene 38 8570183
2016 The Csk-Associated Adaptor PAG Inhibits Effector T Cell Activation in Cooperation with Phosphatase PTPN22 and Dok Adaptors. Cell reports 37 27926878
2009 The C-terminal Src inhibitory kinase (Csk)-mediated tyrosine phosphorylation is a novel molecular mechanism to limit P2X3 receptor function in mouse sensory neurons. The Journal of biological chemistry 36 19509283
2006 Csk-binding protein (Cbp) negatively regulates epidermal growth factor-induced cell transformation by controlling Src activation. Oncogene 36 16636672
1996 Analysis of CSK homologous kinase (CHK/HYL) in hematopoiesis by utilizing gene knockout mice. Biochemical and biophysical research communications 36 8694808
2003 Activation of C-terminal Src kinase (Csk) by phosphorylation at serine-364 depends on the Csk-Src homology 3 domain. The Biochemical journal 35 12600271
1996 Detection of a physical and functional interaction between Csk and Lck which involves the SH2 domain of Csk and is mediated by autophosphorylation of Lck on tyrosine 394. The Journal of biological chemistry 35 8631775
1994 Two distinct protein isoforms are encoded by ntk, a csk-related tyrosine protein kinase gene. Oncogene 35 7970703
2018 Maintenance of murine platelet homeostasis by the kinase Csk and phosphatase CD148. Blood 34 29301754
2001 Nucleotide release and associated conformational changes regulate function in the COOH-terminal Src kinase, Csk. Biochemistry 34 11551213
2006 Docking-based substrate recognition by the catalytic domain of a protein tyrosine kinase, C-terminal Src kinase (Csk). The Journal of biological chemistry 33 16439366
2005 Modulation of TLR signalling by the C-terminal Src kinase (Csk) in macrophages. Genes to cells : devoted to molecular & cellular mechanisms 33 15773898
1994 Rapid and efficient purification of Src homology 2 domain-containing proteins: Fyn, Csk and phosphatidylinositol 3-kinase p85. The Biochemical journal 33 7524477
2003 Mechanism of Csk-mediated down-regulation of Src family tyrosine kinases in epidermal growth factor signaling. The Journal of biological chemistry 32 14613929
1997 Sequence specificity of C-terminal Src kinase (CSK)--a comparison with Src-related kinases c-Fgr and Lyn. European journal of biochemistry 32 9208935
2008 Translational control of C-terminal Src kinase (Csk) expression by PRL3 phosphatase. The Journal of biological chemistry 31 18268019
2006 Negative regulation of T-cell receptor activation by the cAMP-PKA-Csk signalling pathway in T-cell lipid rafts. Frontiers in bioscience : a journal and virtual library 31 16720365
1992 Spleen protein tyrosine kinases TPK-IIB and CSK display different immunoreactivity and opposite specificities toward c-src-derived peptides. FEBS letters 31 1280230
2017 TRAF3 enhances TCR signaling by regulating the inhibitors Csk and PTPN22. Scientific reports 30 28522807
2005 CSK negatively regulates nerve growth factor induced neural differentiation and augments AKT kinase activity. Experimental cell research 30 15890337
2001 The COOH-terminal Src kinase Csk is a tumor antigen in human carcinoma. Cancer research 30 11245444
2001 Protein tyrosine kinase Csk-catalyzed phosphorylation of Src containing unnatural tyrosine analogues. Journal of the American Chemical Society 30 11552794
2001 Novel mechanism of regulation of the non-receptor protein tyrosine kinase Csk: insights from NMR mapping studies and site-directed mutagenesis. Journal of molecular biology 30 11724538
2015 PSTPIP2, a Protein Associated with Autoinflammatory Disease, Interacts with Inhibitory Enzymes SHIP1 and Csk. Journal of immunology (Baltimore, Md. : 1950) 29 26304991
2000 In vitro and in vivo suppression of osteoclast function by adenovirus vector-induced csk gene. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 29 10646113
1994 Regulation of c-Fgr protein kinase by c-Src kinase (CSK) and by polycationic effectors. The Journal of biological chemistry 29 7515063
2023 Adipsin alleviates cardiac microvascular injury in diabetic cardiomyopathy through Csk-dependent signaling mechanism. BMC medicine 28 37237266
2013 The tyrosine kinase CSK associates with FLT3 and c-Kit receptors and regulates downstream signaling. Cellular signalling 28 23707526
2011 Down-regulation of the tumor suppressor C-terminal Src kinase (Csk)-binding protein (Cbp)/PAG1 is mediated by epigenetic histone modifications via the mitogen-activated protein kinase (MAPK)/phosphatidylinositol 3-kinase (PI3K) pathway. The Journal of biological chemistry 28 21388951
2010 A PKA-Csk-pp60Src signaling pathway regulates the switch between endothelial cell invasion and cell-cell adhesion during vascular sprouting. Blood 28 20826718
2008 The Csk-binding protein PAG regulates PDGF-induced Src mitogenic signaling via GM1. The Journal of cell biology 28 18695048
1994 IL-4 and IL-13 induce Lsk, a Csk-like tyrosine kinase, in human monocytes. The Journal of experimental medicine 27 7964512
2000 The Src/Csk regulatory circuit arose early in metazoan evolution. Oncogene 26 10951585
2010 Structural elements and allosteric mechanisms governing regulation and catalysis of CSK-family kinases and their inhibition of Src-family kinases. Growth factors (Chur, Switzerland) 25 20476842
2003 C-terminal Src kinase (CSK) modulates insulin-like growth factor-I signaling through Src in 3T3-L1 differentiation. Endocrinology 25 12746317
2007 Proteomic identification of ZO-1/2 as a novel scaffold for Src/Csk regulatory circuit. Biochemical and biophysical research communications 24 18086565
2003 Functions of the activation loop in Csk protein-tyrosine kinase. The Journal of biological chemistry 24 12686554
1997 Csk overexpression reduces several monokines and nitric oxide productions but enhances prostaglandin E2 production in response to lipopolysaccharide in the macrophage cell line J774A.1. European journal of immunology 24 9079817

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