Affinage

TEC

Tyrosine-protein kinase Tec · UniProt P42680

Length
631 aa
Mass
73.6 kDa
Annotated
2026-04-28
100 papers in source corpus 25 papers cited in narrative 25 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TEC is a non-receptor tyrosine kinase of the Tec/Btk family that functions as a signal amplifier downstream of cytokine receptors, antigen receptors, ITAM-coupled receptors, and G-protein-coupled receptors, coupling PI3K-generated PtdIns(3,4,5)P3 signals to PLCγ-dependent calcium mobilization and transcriptional responses in hematopoietic and other cell types. Its PH domain binds PtdIns(3,4,5)P3 for membrane recruitment where Src family kinases activate it; TEC then phosphorylates PLCγ to drive IP3 production and sustained Ca²⁺ entry, a pathway negatively regulated by SHIP1/2-mediated PtdIns(3,4,5)P3 hydrolysis and by intramolecular SH3-PRR autoinhibition (PMID:9524119, PMID:15492005, PMID:11684687). Beyond canonical PLCγ signaling, TEC phosphorylates FGF2 to promote its unconventional secretion, phosphorylates PLK4 to stabilize it and regulate cell invasion, and forms RANK-ITAM signaling complexes with BLNK/SLP-76 essential for osteoclastogenesis—Btk/Tec double-knockout mice exhibit severe osteopetrosis (PMID:27382052, PMID:34637843, PMID:18329366). Catalytic activity is allosterically controlled by an extended regulatory spine that transmits signals from a conserved SH2-kinase linker tryptophan to the active site, and gatekeeper mutations constitutively activate the kinase (PMID:20826165, PMID:27010561).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1990 Medium

    Identifying TEC as a novel non-receptor tyrosine kinase established that a Src-related kinase with preferential hepatic expression existed outside canonical Src/Abl families, opening the question of its signaling role.

    Evidence cDNA library screening with v-fps kinase probe and sequence analysis in liver

    PMID:2284097

    Open questions at the time
    • No functional data beyond sequence; tissue expression limited to RNA level
    • Substrates and activating signals unknown
  2. 1995 High

    Demonstrating that TEC associates with gp130 and is activated by IL-6 family cytokines placed TEC as a downstream effector of JAK-coupled cytokine receptor signaling, distinct from Btk.

    Evidence Co-immunoprecipitation and in vitro kinase assay upon cytokine stimulation in pro-B cells

    PMID:7530500

    Open questions at the time
    • Direct substrates of TEC in the gp130 pathway not identified
    • Mechanism of TEC recruitment to receptor complex unclear
  3. 1996 Medium

    Showing that SH3 domain deletion constitutively activates TEC revealed an intramolecular autoinhibitory mechanism, raising the question of how autoinhibition is structurally mediated.

    Evidence SH3 deletion mutant expression in 293 and BA/F3 cells with kinase activity assay

    PMID:9045937

    Open questions at the time
    • Structural basis of SH3-mediated autoinhibition not resolved
    • Whether the SH3 domain acts through intramolecular or intermolecular contacts was unclear
  4. 1997 Medium

    Identifying TEC interactions with PI3K p85 subunit, Vav, and JAK1 positioned TEC at a signaling nexus between JAK/STAT, PI3K, and Rho/Rac pathways.

    Evidence Yeast two-hybrid and co-immunoprecipitation in cytokine-stimulated cells

    PMID:9178903

    Open questions at the time
    • Functional consequence of PI3K-TEC complex not established
    • Whether Vav is a substrate or scaffold for TEC was unresolved
  5. 1998 High

    Three contemporaneous studies established the core signaling axis: PtdIns(3,4,5)P3 recruits TEC via its PH domain, TEC phosphorylates PLCγ to produce IP3 and drive sustained Ca²⁺ mobilization downstream of antigen receptors, and SHIP terminates the signal—defining TEC as a PI3K-to-PLCγ relay.

    Evidence PH domain-lipid binding assays, in vitro PLCγ phosphorylation, IP3 measurement, calcium flux in Btk-deficient B cells, Rho-dependent SRF reporter assays

    PMID:9524119 PMID:9524120 PMID:9755164

    Open questions at the time
    • Whether TEC and Btk are fully redundant in B cells was unresolved
    • Structural basis of PH domain selectivity for PtdIns(3,4,5)P3 not determined
  6. 1999 High

    Identification of adaptor selectivity (SLP-65/SLP-76 binding via TEC SH2 domain), functional redundancy with Btk in DT40 cells, and BRDG1 as a TEC-specific substrate revealed how TEC is recruited to signaling complexes and expanded its substrate repertoire.

    Evidence SH2 domain binding assays, reconstitution in Btk-deficient DT40 B cells, yeast two-hybrid and in vitro kinase assays for BRDG1

    PMID:10224128 PMID:10518561 PMID:10556826

    Open questions at the time
    • In vivo physiological role of BRDG1 phosphorylation not tested in knockout models
    • Degree of functional overlap between TEC and Btk in primary cells not fully defined
  7. 2000 High

    Demonstrating TEC activation downstream of SCF/cKit (forming a Lyn-Dok-1 complex) and GPVI/CD32 in platelets broadened TEC's receptor repertoire beyond cytokine and antigen receptors to growth factor and ITAM-coupled receptors.

    Evidence Co-IP and kinase assays in hematopoietic cells (SCF stimulation); phosphospecific antibodies in platelets (GPVI/CD32 stimulation)

    PMID:10688822 PMID:11071635

    Open questions at the time
    • Platelet-specific substrates of TEC not identified
    • Physiological consequence of TEC activation in platelet aggregation not tested in vivo
  8. 2001 High

    The NMR structure of the TEC SH3 domain with mapping of two PRR-binding sites resolved how intramolecular versus intermolecular SH3-PRR contacts control autoinhibition and targeting, while identification of Sak/PLK4 as a TEC substrate linked TEC to cell cycle regulation.

    Evidence NMR structure determination with mutagenesis and binding assays; yeast two-hybrid and in vitro kinase assay for Sak

    PMID:11489907 PMID:11684687

    Open questions at the time
    • Full-length TEC structure including SH3-PRR interaction not available
    • In vivo relevance of TEC-Sak interaction not confirmed in knockout models
  9. 2004 High

    Identifying SHIP1/SHIP2 as preferential negative regulators of TEC (via SH3-mediated interaction and PtdIns(3,4,5)P3 degradation) and PKCθ as a TEC-dependent signaling partner in T cells defined cell-type-specific regulatory inputs.

    Evidence Co-IP, kinase assay, membrane localization rescue (SHIP); Co-IP, dominant-negative, reporter assay (PKCθ) in T cells

    PMID:15214048 PMID:15492005

    Open questions at the time
    • Whether SHIP directly dephosphorylates TEC or only removes PtdIns(3,4,5)P3 was not resolved
    • PKCθ-TEC interaction awaits structural characterization
  10. 2007 High

    Quantitative biochemistry established that the SH2-kinase linker allosterically activates catalysis and that TEC uses a remote SH2 domain docking mechanism on substrates like PLCγ, explaining how substrate selectivity is achieved.

    Evidence In vitro kinase assays with linker mutagenesis and SH2 domain deletion/competition kinetics

    PMID:17425330 PMID:17439160

    Open questions at the time
    • No crystal structure capturing the linker-kinase allosteric interface
    • Whether SH2-docking mechanism operates for all TEC substrates (e.g., BRDG1, Sak) not tested
  11. 2008 High

    Btk/Tec double-knockout mice revealed a non-redundant physiological role in osteoclastogenesis via RANK-ITAM-PLCγ calcium signaling, and TEC was shown to mediate innate immune responses to MSU crystals in neutrophils.

    Evidence Genetic double-KO mice with bone histology, Co-IP of RANK/BLNK complex; siRNA knockdown with cytokine ELISA in neutrophils

    PMID:18329366 PMID:18512796

    Open questions at the time
    • Relative contribution of TEC versus Btk in single-KO osteoclasts not fully dissected
    • MSU-induced TEC activation mechanism upstream of Src not resolved
  12. 2010 High

    Discovery of the extended regulatory spine network explained how distal regulatory inputs (SH2-kinase linker tryptophan, C-helix methionine, gatekeeper residue) are transmitted allosterically to the TEC catalytic site.

    Evidence Mutagenesis of regulatory spine residues with in vitro kinase assay and structural analysis

    PMID:20826165

    Open questions at the time
    • Full-length TEC structure showing regulatory spine in intact protein context not available
    • Whether pharmacological spine disruption can selectively inhibit TEC not tested
  13. 2016 High

    TEC was shown to directly phosphorylate FGF2 on tyrosine residues to promote membrane pore formation and unconventional secretion, establishing a non-immune function for TEC in growth factor export.

    Evidence In vitro kinase assay, Co-IP, FGF2 secretion assay with small molecule inhibitors

    PMID:27382052

    Open questions at the time
    • Identity of the specific FGF2 tyrosine residues phosphorylated by TEC not mapped
    • In vivo relevance of TEC-FGF2 axis not tested in animal models
  14. 2021 Medium

    TEC was found to phosphorylate PLK4 at Y86, stabilizing PLK4 protein and promoting HCC cell invasion through FAK signaling, extending TEC's substrate repertoire to cancer cell migration.

    Evidence In vitro kinase assay, Y86 mutagenesis, protein stability assay, HCC cell invasion assays

    PMID:34637843

    Open questions at the time
    • In vivo validation in animal tumor models not reported
    • Whether TEC-PLK4 interaction occurs in non-cancer contexts is unknown
    • Single-lab finding

Open questions

Synthesis pass · forward-looking unresolved questions
  • A full-length structure of TEC capturing the autoinhibited-to-active transition, the relative contributions of TEC versus Btk in specific immune cell lineages in vivo, and the physiological significance of non-immune TEC substrates (FGF2, PLK4) remain unresolved.
  • No full-length TEC crystal/cryo-EM structure available
  • Single-KO TEC mouse phenotype in immune cells incompletely characterized relative to Btk
  • In vivo roles of TEC-FGF2 and TEC-PLK4 axes untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 10 GO:0016740 transferase activity 6 GO:0008289 lipid binding 1
Localization
GO:0005886 plasma membrane 2 GO:0005829 cytosol 1
Pathway
R-HSA-168256 Immune System 7 R-HSA-162582 Signal Transduction 6
Partners
BLNKDOK1LYNPLCG1PLCG2SHIP1SHIP2SLP76
Complex memberships
RANK-ITAM-BLNK/SLP-76 signaling complex

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1990 TEC was identified as a novel non-receptor protein-tyrosine kinase preferentially expressed in liver, with its C-terminal domain sharing significant homology with Src family kinase catalytic domains. cDNA library screening with v-fps kinase domain probe, nucleotide sequence analysis Oncogene Medium 2284097
1995 TEC kinase associates with and is activated by gp130, the signal-transducing subunit of the IL-6 family cytokine receptors; IL-3 and G-CSF also activate Tec (but not Btk) in pro-B cells, establishing TEC as a component of gp130-linked signaling. Co-immunoprecipitation, in vitro kinase assay, stimulation of cell lines with cytokines Blood High 7530500
1996 Deletion of the SH3 domain of TEC results in a constitutively hyperphosphorylated and activated kinase, indicating the SH3 domain negatively regulates TEC kinase activity. SH3 domain deletion mutant expression in 293 cells and hematopoietic BA/F3 cells, kinase activity assay Japanese journal of cancer research Medium 9045937
1997 TEC associates with the p85 and p55 subunits of PI-3 kinase (interaction dependent on Tec kinase activity and requiring the SH2-kinase domain), and with Vav through its SH2 domain (kinase-independent); JAK1 associates with Tec and upon cytokine stimulation Tec and p85-PI3K associate in mammalian cells. Yeast two-hybrid, co-immunoprecipitation in cytokine-stimulated cells Oncogene Medium 9178903
1998 PtdIns(3,4,5)P3 interacting with the PH domain of TEC family kinases acts as an upstream activation signal, leading to TEC kinase-dependent PLCγ tyrosine phosphorylation and IP3 production; SHIP-mediated degradation of PtdIns(3,4,5)P3 blocks this pathway. Direct PH domain-lipid binding assay, in vitro PLCγ phosphorylation assay, inositol trisphosphate measurement in cells The EMBO journal High 9524119
1998 TEC/Btk family kinases regulate sustained intracellular Ca2+ increases following BCR activation by controlling IP3-gated calcium store depletion and store-operated calcium entry; Btk/Tec and PLCγ co-expression leads to PLCγ tyrosine phosphorylation. Ectopic expression in Btk-deficient B-cell lines, calcium flux measurement, IP3 assay, co-expression studies The EMBO journal High 9524120
1998 TEC and Bmx activate serum response factor (SRF) in synergy with constitutively active Gα12/13 subunits in a Rho-dependent manner; kinase and TH domains of TEC are required for SRF activation; Gα12/13 stimulates autophosphorylation and transphosphorylation activities of Tec. Transient transfection in NIH 3T3 cells, SRF luciferase reporter, C3 toxin inhibition, kinase activity assay The EMBO journal Medium 9755164
1999 The SH2 domain of TEC (and Btk/Itk) exhibits restricted binding specificity, selectively binding tyrosine-phosphorylated SLP-65 (in B cells) or SLP-76 (in T cells) upon antigen receptor activation, which is required for PLCγ phosphorylation. SH2 domain binding assay, co-immunoprecipitation from activated lymphocytes European journal of immunology Medium 10556826
1999 TEC (but not Btk) can reconstitute PLCγ2-dependent calcium mobilization, ERK/MAPK activation, and apoptosis in Btk-deficient DT40 B cells, demonstrating a common signaling function for Tec kinases as amplifiers of PLCγ2-dependent signal transduction. Reconstitution in Btk-deficient DT40 B cells, calcium flux assay, ERK activation, apoptosis assay The Journal of biological chemistry High 10224128
1999 BRDG1 (BCR downstream signaling 1) was identified as a docking protein acting downstream of TEC; Tec (but not Btk) directly phosphorylates BRDG1 in vitro and in cells; this requires the PH and SH2 domains as well as the kinase domain of Tec; BRDG1 participates in a positive feedback loop increasing Tec activity. Yeast two-hybrid, in vitro kinase assay, co-expression in 293 cells, domain deletion analysis, BCR stimulation Proceedings of the National Academy of Sciences of the United States of America High 10518561
2000 SCF/cKit signaling activates Tec in a PI3K-dependent manner; Tec forms a stable complex with Lyn and Dok-1 (p62Dok-1); the Tec homology and SH2 domains of Tec are required for Dok-1 interaction; Tec and Lyn phosphorylate Dok-1, which then scaffolds additional signaling molecules. Co-immunoprecipitation, domain deletion, in vitro kinase assay, inhibitor studies in hematopoietic cells Blood High 11071635
2000 TEC and Btk are activated by tyrosine phosphorylation in platelets upon collagen receptor (GPVI) stimulation or CD32 cross-linking via a mechanism involving ITAM, Src family kinases, and PI3-kinase; in XLA (Btk-deficient) platelets, Tec undergoes compensatory activation. Phosphopeptide-specific antibodies, kinase activity assay, kinetic analysis with inhibitors in human platelets Blood Medium 10688822
2001 The solution structure of the TEC SH3 domain was determined; the proline-rich region (PRR) of Tec contains two SH3-binding sites: site 1 (KTLPPAP) binds intramolecularly to the SH3 domain, while site 2 (KRRPPPPIPP) can only bind intermolecularly, suggesting distinct roles in kinase targeting and enzyme activation. NMR structure determination, site-directed mutagenesis, in vitro binding assays The Journal of biological chemistry High 11684687
2001 Sak serine-threonine kinase (a Polo-like kinase family member) is phosphorylated by TEC on tyrosine residues, and Sak serine-threonine kinase activity is only detectable in the presence of Tec; Tec also protects Sak from PEST-sequence-dependent proteolysis. Yeast two-hybrid, co-expression in 293 cells, in vitro kinase assay, stability/degradation assay The Journal of biological chemistry Medium 11489907
2002 The proline-rich region (PRR) in the Tec homology domain of ITK (a closely related Tec family member) positively regulates basal kinase activity and the response to Src family kinase (Lck) activation; the SH3 domain negatively regulates ITK basal activity. Domain deletion mutants, kinase activity assay, PLCγ1 phosphorylation readout in Jurkat cells FEBS letters Medium 12163161
2004 SHIP1 and SHIP2 interact preferentially with TEC (compared to other Tec family members) via the Tec SH3 domain, and negatively regulate Tec by inhibiting its kinase activity and membrane localization through dephosphorylation of local PtdIns(3,4,5)P3. Co-immunoprecipitation, kinase activity assay, membrane localization assay, constitutive membrane-targeting rescue experiment The Journal of biological chemistry High 15492005
2004 TEC constitutively associates with PKCθ via its pleckstrin-homology domain; PKCθ-initiated signaling requires Tec (but not Itk or Rlk) to activate AP-1 and PLCγ1/Ca2+ signaling in restimulated T cells; a dominant-negative Tec blocks PKCθ-induced AP-1 activation. Co-immunoprecipitation, dominant-negative expression, luciferase reporter assay, calcium mobilization in primary T cells European journal of immunology Medium 15214048
2007 The short linker region flanked by the SH2 and kinase domains of Tec kinases positively regulates catalytic activity; specific conserved residues in this linker allosterically regulate kinase activity, a mechanism conserved across Tec family members. Quantitative in vitro kinase assay, mutagenesis of linker residues in Itk (Tec family model) Biochemistry High 17425330
2007 TEC (and Btk) use a remote SH2 domain-dependent substrate docking mechanism: the SH2 domain of substrates (PLCγ1, Itk itself) is required for efficient tyrosine phosphorylation; a stable interaction occurs between substrate SH2 domains and the Tec kinase domain. In vitro kinase assay with SH2 domain deletion/competition, kinetic analysis with SH2-peptide fusion substrates Biochemistry High 17439160
2008 TEC and Btk tyrosine kinases link RANK and ITAM signaling in osteoclasts by forming a Btk(Tec)/BLNK(SLP-76)-containing complex, leading to PLCγ-mediated calcium signaling essential for osteoclast differentiation; mice lacking both Btk and Tec show severe osteopetrosis due to defective osteoclastogenesis. Genetic knockout (Btk/Tec double-deficient mice), co-immunoprecipitation of signaling complex, PLCγ activation assay, calcium measurement, bone histology Cell High 18329366
2008 TEC kinase is activated in neutrophils in a Src-dependent manner upon MSU crystal stimulation; Tec activation is required for MSU crystal-induced IL-1β and IL-8 secretion and generation of chemotactic activity; colchicine inhibits Tec tyrosine phosphorylation. Immunoprecipitation, immunoblotting, siRNA knockdown of Tec, ELISA for cytokines, chemotaxis assay Arthritis and rheumatism Medium 18512796
2010 An allosteric signaling network ('extended regulatory spine') within Tec kinases was identified that transmits regulatory signals from the SH2-kinase linker tryptophan and a conserved methionine in the C-helix to the catalytic domain; mutation of the gatekeeper residue constitutively activates the kinase by pre-assembling the regulatory spine. In vitro kinase assay, mutagenesis of regulatory spine residues, structural analysis Journal of molecular biology High 20826165
2016 TEC kinase directly interacts with FGF2 and phosphorylates FGF2 on tyrosine residues, stimulating FGF2 membrane pore formation required for unconventional secretion; small molecule inhibitors of the FGF2-Tec interaction block FGF2 tyrosine phosphorylation and its unconventional secretion in cells. In vitro kinase assay, co-immunoprecipitation, small molecule inhibitor studies, FGF2 secretion assay in cells The Journal of biological chemistry High 27382052
2016 Dynamic allostery in Tec family kinases is mediated by a conserved tryptophan in the N-terminal 17-residue SH2-kinase linker; mutation of this tryptophan to alanine completely abolishes kinase activity; specific tryptophan side-chain rotamers promote coordinated motions across the kinase domain. Hydrogen/deuterium exchange mass spectrometry, molecular dynamics simulations, mutagenesis, in vitro kinase assay PLoS computational biology High 27010561
2021 TEC tyrosine kinase directly phosphorylates PLK4 at tyrosine 86, stabilizing PLK4 protein and enhancing PLK4-mediated HCC cell invasion; TEC promotes PLK4-mediated phosphorylation of focal adhesion kinase to regulate focal adhesion signaling in HCC cell migration. In vitro kinase assay, site-directed mutagenesis (Y86 of PLK4), protein stability assay, transcriptome sequencing, HCC cell migration/invasion assay Cancer letters Medium 34637843

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 Phosphatidylinositol-3,4,5-trisphosphate (PtdIns-3,4,5-P3)/Tec kinase-dependent calcium signaling pathway: a target for SHIP-mediated inhibitory signals. The EMBO journal 353 9524119
1998 Btk/Tec kinases regulate sustained increases in intracellular Ca2+ following B-cell receptor activation. The EMBO journal 323 9524120
2005 Tec family kinases in T lymphocyte development and function. Annual review of immunology 272 15771581
2008 Tyrosine kinases Btk and Tec regulate osteoclast differentiation by linking RANK and ITAM signals. Cell 250 18329366
2001 The Tec family of cytoplasmic tyrosine kinases: mammalian Btk, Bmx, Itk, Tec, Txk and homologs in other species. BioEssays : news and reviews in molecular, cellular and developmental biology 237 11340625
1997 Regulatory intramolecular association in a tyrosine kinase of the Tec family. Nature 234 8985255
2010 T-cell signaling regulated by the Tec family kinase, Itk. Cold Spring Harbor perspectives in biology 213 20519342
2010 The Src, Syk, and Tec family kinases: distinct types of molecular switches. Cellular signalling 200 20206686
1999 Interaction of SLP adaptors with the SH2 domain of Tec family kinases. European journal of immunology 198 10556826
2006 Altered development of CD8+ T cell lineages in mice deficient for the Tec kinases Itk and Rlk. Immunity 159 16860760
2006 The Tec family tyrosine kinases Itk and Rlk regulate the development of conventional CD8+ T cells. Immunity 154 16860759
1990 A novel protein-tyrosine kinase, tec, is preferentially expressed in liver. Oncogene 153 2284097
2019 Thymic epithelial cell heterogeneity: TEC by TEC. Nature reviews. Immunology 147 31804611
2001 Mutation of Tec family kinases alters T helper cell differentiation. Nature immunology 147 11702066
1995 Association and activation of Btk and Tec tyrosine kinases by gp130, a signal transducer of the interleukin-6 family of cytokines. Blood 146 7530500
2005 TEC-family kinases: regulators of T-helper-cell differentiation. Nature reviews. Immunology 135 15803148
2010 Structures of human Bruton's tyrosine kinase in active and inactive conformations suggest a mechanism of activation for TEC family kinases. Protein science : a publication of the Protein Society 124 20052711
2019 PF-06651600, a Dual JAK3/TEC Family Kinase Inhibitor. ACS chemical biology 122 31082193
2007 Signalling through TEC kinases regulates conventional versus innate CD8(+) T-cell development. Nature reviews. Immunology 117 17479128
1999 Tec family of protein-tyrosine kinases: an overview of their structure and function. Cytokine & growth factor reviews 117 10647781
1999 Fusion of the EWS-related gene TAF2N to TEC in extraskeletal myxoid chondrosarcoma. Cancer research 114 10537274
2009 Tec kinases regulate T-lymphocyte development and function: new insights into the roles of Itk and Rlk/Txk. Immunological reviews 112 19290923
2000 Tec family kinases modulate thresholds for thymocyte development and selection. The Journal of experimental medicine 102 11015440
2008 The tec family tyrosine kinase Btk Regulates RANKL-induced osteoclast maturation. The Journal of biological chemistry 95 18281276
1994 TXK, a novel human tyrosine kinase expressed in T cells shares sequence identity with Tec family kinases and maps to 4p12. Human molecular genetics 84 7951233
2000 Rapid tyrosine phosphorylation and activation of Bruton's tyrosine/Tec kinases in platelets induced by collagen binding or CD32 cross-linking. Blood 82 10688822
2000 Stem cell factor induces phosphatidylinositol 3'-kinase-dependent Lyn/Tec/Dok-1 complex formation in hematopoietic cells. Blood 82 11071635
1998 Tec/Bmx non-receptor tyrosine kinases are involved in regulation of Rho and serum response factor by Galpha12/13. The EMBO journal 81 9755164
2002 Beyond calcium: new signaling pathways for Tec family kinases. Journal of cell science 80 12118060
2004 Requirement for Tec kinases in chemokine-induced migration and activation of Cdc42 and Rac. Current biology : CB 79 15186750
1997 Tec tyrosine kinase links the cytokine receptors to PI-3 kinase probably through JAK. Oncogene 76 9178903
2001 Tec kinases: modulators of lymphocyte signaling and development. Current opinion in immunology 75 11406363
1999 The EWS/TEC fusion protein encoded by the t(9;22) chromosomal translocation in human chondrosarcomas is a highly potent transcriptional activator. Oncogene 74 10359536
2004 The role of Tec family kinases in myeloid cells. International archives of allergy and immunology 73 15133303
1999 Txk, a nonreceptor tyrosine kinase of the Tec family, is expressed in T helper type 1 cells and regulates interferon gamma production in human T lymphocytes. The Journal of experimental medicine 70 10523612
1998 SRC64 regulates the localization of a Tec-family kinase required for Drosophila ring canal growth. Molecular cell 69 9660966
2002 New insights into the regulation and functions of Tec family tyrosine kinases in the immune system. Current opinion in immunology 68 11973131
2003 Chemotactic factor-induced recruitment and activation of Tec family kinases in human neutrophils. II. Effects of LFM-A13, a specific Btk inhibitor. Journal of immunology (Baltimore, Md. : 1950) 67 12734372
2000 A specific intermolecular association between the regulatory domains of a Tec family kinase. Journal of molecular biology 67 10986122
2020 Efficacy and Safety of PF-06651600 (Ritlecitinib), a Novel JAK3/TEC Inhibitor, in Patients With Moderate-to-Severe Rheumatoid Arthritis and an Inadequate Response to Methotrexate. Arthritis & rheumatology (Hoboken, N.J.) 66 32419304
2003 The role of Tec family kinases in T cell development and function. Immunological reviews 66 12614356
2004 Regulation of CXC chemokine receptor 4-mediated migration by the Tec family tyrosine kinase ITK. The Journal of biological chemistry 64 15123627
1996 Functional LCK Is required for optimal CD28-mediated activation of the TEC family tyrosine kinase EMT/ITK. The Journal of biological chemistry 64 8636141
2009 The Tec kinases Itk and Rlk regulate conventional versus innate T-cell development. Immunological reviews 63 19290924
2012 Tec family kinases in inflammation and disease. International reviews of immunology 60 22449071
1993 Elimination of Tec elements involves a novel excision process. Genes & development 60 8380782
2004 Positive feedback regulation of PLCgamma1/Ca(2+) signaling by PKCtheta in restimulated T cells via a Tec kinase-dependent pathway. European journal of immunology 55 15214048
2002 Chemotactic factor-induced recruitment and activation of Tec family kinases in human neutrophils. Implication of phosphatidynositol 3-kinases. The Journal of biological chemistry 52 11940595
1999 Reconstitution of Btk signaling by the atypical tec family tyrosine kinases Bmx and Txk. The Journal of biological chemistry 52 10224128
2007 Tec kinases in T cell and mast cell signaling. Advances in immunology 51 17383541
2007 Tec kinases, actin, and cell adhesion. Immunological reviews 51 17624943
1999 Molecular cloning of a docking protein, BRDG1, that acts downstream of the Tec tyrosine kinase. Proceedings of the National Academy of Sciences of the United States of America 49 10518561
1997 In vitro inhibition of endothelial cell growth by the antiangiogenic drug AGM-1470 (TNP-470) and the anti-endoglin antibody TEC-11. Anti-cancer drugs 48 9095328
2010 DKK1 mediated inhibition of Wnt signaling in postnatal mice leads to loss of TEC progenitors and thymic degeneration. PloS one 47 20161711
2016 Dynamic Allostery Mediated by a Conserved Tryptophan in the Tec Family Kinases. PLoS computational biology 43 27010561
2009 The role of Tec family kinases in mononuclear phagocytes. Critical reviews in immunology 42 19673686
2005 Signaling through CD16b in human neutrophils involves the Tec family of tyrosine kinases. Journal of leukocyte biology 42 15899983
2007 The linker between SH2 and kinase domains positively regulates catalysis of the Tec family kinases. Biochemistry 41 17425330
2004 SHIP family inositol phosphatases interact with and negatively regulate the Tec tyrosine kinase. The Journal of biological chemistry 41 15492005
2005 Tec kinases regulate TCR-mediated recruitment of signaling molecules and integrin-dependent cell adhesion. Journal of immunology (Baltimore, Md. : 1950) 40 16237085
2024 Integrated Safety Analysis of Ritlecitinib, an Oral JAK3/TEC Family Kinase Inhibitor, for the Treatment of Alopecia Areata from the ALLEGRO Clinical Trial Program. American journal of clinical dermatology 39 38263353
2011 Tec family kinases: regulation of FcεRI-mediated mast-cell activation. The FEBS journal 39 21362140
2006 Skewed Th1 responses caused by excessive expression of Txk, a member of the Tec family of tyrosine kinases, in patients with Behcet's disease. Clinical medicine & research 38 16809408
2004 Tec kinases: shaping T-cell activation through actin. Trends in cell biology 37 15308211
2001 Sak serine-threonine kinase acts as an effector of Tec tyrosine kinase. The Journal of biological chemistry 36 11489907
2000 Protein-tyrosine phosphatase D1, a potential regulator and effector for Tec family kinases. The Journal of biological chemistry 35 11013262
1999 The Tec family protein-tyrosine kinases: a subset of kinases for a subset of signalings. International journal of hematology 35 10641436
1996 CD2 signaling in T cells involves tyrosine phosphorylation and activation of the Tec family kinase, EMT/ITK/TSK. International immunology 35 8943565
2007 A remote substrate docking mechanism for the tec family tyrosine kinases. Biochemistry 34 17439160
2010 Identification of an allosteric signaling network within Tec family kinases. Journal of molecular biology 33 20826165
2001 The solution structure and intramolecular associations of the Tec kinase SRC homology 3 domain. The Journal of biological chemistry 31 11684687
2022 Regulation of the Tec family of non-receptor tyrosine kinases in cardiovascular disease. Cell death discovery 30 35296647
2023 Improvements in immune/melanocyte biomarkers with JAK3/TEC family kinase inhibitor ritlecitinib in vitiligo. The Journal of allergy and clinical immunology 29 37777018
2022 The monomer TEC of blueberry improves NASH by augmenting tRF-47-mediated autophagy/pyroptosis signaling pathway. Journal of translational medicine 29 35287671
2016 Small Molecule Inhibitors Targeting Tec Kinase Block Unconventional Secretion of Fibroblast Growth Factor 2. The Journal of biological chemistry 29 27382052
1999 Pleckstrin homology domains of tec family protein kinases. Biochemical and biophysical research communications 29 10548506
2008 Crystal-induced neutrophil activation: X. Proinflammatory role of the tyrosine kinase Tec. Arthritis and rheumatism 28 18512796
2018 Multidomain Control Over TEC Kinase Activation State Tunes the T Cell Response. Annual review of immunology 27 29677469
2008 Phylogeny of Tec family kinases identification of a premetazoan origin of Btk, Bmx, Itk, Tec, Txk, and the Btk regulator SH3BP5. Advances in genetics 27 19161832
2014 The accessory factor Nef links HIV-1 to Tec/Btk kinases in an Src homology 3 domain-dependent manner. The Journal of biological chemistry 26 24722985
2011 Tec family kinases: Itk signaling and the development of NKT αβ and γδ T cells. The FEBS journal 26 21362141
1998 Platelet collection with the Amicus and the AS.TEC 204 blood cell separators. Transfusion 25 9563409
2012 Regulation of T-cell responses and disease by tec kinase Itk. International reviews of immunology 24 22449075
2020 Activation of the Tec Kinase ITK Controls Graded IRF4 Expression in Response to Variations in TCR Signal Strength. Journal of immunology (Baltimore, Md. : 1950) 23 32493815
2013 The Tec kinase ITK regulates thymic expansion, emigration, and maturation of γδ NKT cells. Journal of immunology (Baltimore, Md. : 1950) 23 23378428
1994 Developmentally regulated, low abundance Tec element transcripts in Euplotes crassus--implications for DNA elimination and transposition. Nucleic acids research 23 7971284
2016 A Tec kinase BTK inhibitor ibrutinib promotes maturation and activation of dendritic cells. Oncoimmunology 22 27471620
2012 DEF6, a novel substrate for the Tec kinase ITK, contains a glutamine-rich aggregation-prone region and forms cytoplasmic granules that co-localize with P-bodies. The Journal of biological chemistry 22 22829599
2021 TEC kinase stabilizes PLK4 to promote liver cancer metastasis. Cancer letters 21 34637843
2002 The Tec family of tyrosine kinases in T cells, amplifiers of T cell receptor signals. The international journal of biochemistry & cell biology 21 12127569
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2021 Effects of the Btk-Inhibitors Remibrutinib (LOU064) and Rilzabrutinib (PRN1008) With Varying Btk Selectivity Over Tec on Platelet Aggregation and in vitro Bleeding Time. Frontiers in cardiovascular medicine 20 34631841
2009 Tec kinases regulate actin assembly and cytokine expression in LPS-stimulated human neutrophils via JNK activation. Cellular immunology 20 19393603
2007 Regulation of oncogenic transcription factor hTAF(II)68-TEC activity by human glyceraldehyde-3-phosphate dehydrogenase (GAPDH). The Biochemical journal 20 17302560
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2023 Nephrotoxicity assessment of podophyllotoxin-induced rats by regulating PI3K/Akt/mTOR-Nrf2/HO1 pathway in view of toxicological evidence chain (TEC) concept. Ecotoxicology and environmental safety 18 37651795
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2019 The Tec kinase ITK is essential for ILC2 survival and epithelial integrity in the intestine. Nature communications 17 30770814
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