Affinage

TEC

Nuclear receptor subfamily 4 group A member 3 · UniProt Q92570

Length
626 aa
Mass
68.2 kDa
Annotated
2026-06-10
100 papers in source corpus 38 papers cited in narrative 38 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

TEC is the founding member of the Tec family of non-receptor protein-tyrosine kinases, originally identified as a Src-homologous kinase preferentially expressed in liver (PMID:2284097), that couples diverse cell-surface receptors to phospholipase Cγ-driven calcium signaling (PMID:9524119). TEC is recruited to the membrane when its PH domain binds PtdIns(3,4,5)P3 generated by PI3K, where it phosphorylates PLCγ to drive IP3 production and Ca2+ mobilization; the SHIP inositol phosphatase opposes this by degrading PtdIns(3,4,5)P3 (PMID:9524119, PMID:15492005). Activation occurs downstream of cytokine receptors, the receptor tyrosine kinase c-Kit, the IL-6-family transducer gp130, antigen and costimulatory receptors, GPCRs, and integrins, with TEC being phosphorylated and activated directly by Lyn (PMID:7526158, PMID:7530500, PMID:8621063, PMID:9652744); in T cells CD28-mediated activation requires Src-family (Lck) activity (PMID:9872994, PMID:10382746). TEC propagates signaling by phosphorylating docking and effector substrates including BRDG1, Dok-1, the Polo-family kinase Sak, and FGF2, the last during unconventional FGF2 secretion (PMID:10518561, PMID:11071635, PMID:11489907, PMID:27382052). In T cells TEC has a unique adapter-independent route to PLCγ/NFAT activation distinct from Itk, acting through a PKCθ→TEC→PLCγ1→Ca2+ feedback loop to drive AP-1 and IL-2 expression (PMID:14993283, PMID:15214048, PMID:9872994). Genetically, TEC acts redundantly with Btk: Btk/Tec double-deficient mice fail at an early stage of B cell development, lose GPVI-dependent platelet activation, and develop severe osteopetrosis through a RANK/ITAM/BLNK(SLP-76)→PLCγ→NFATc1 osteoclastogenic complex (PMID:11104803, PMID:12842985, PMID:18329366). TEC also drives Fcγ-receptor phagocytosis and assembly of the noncanonical caspase-8 inflammasome downstream of Dectin-1/Syk during fungal infection (PMID:18566394, PMID:25474208). TEC activity is held in check by intramolecular SH3–proline-rich interactions and an extended regulatory spine relaying allosteric signals from the SH2-kinase linker to the catalytic domain (PMID:11684687, PMID:17425330, PMID:20826165), and is negatively regulated by SOCS-1, SHIP1/2, and Dok-1/2 (PMID:9341160, PMID:15492005, PMID:14647425).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1990 Medium

    Establishing that a distinct non-receptor tyrosine kinase existed defined the founding member of a new kinase family and set the stage for its functional dissection.

    Evidence cDNA cloning with a v-fps kinase probe and Northern expression analysis in liver

    PMID:2284097

    Open questions at the time
    • No catalytic substrate or signaling pathway identified
    • Function beyond sequence homology unknown
  2. 1994 High

    Linking TEC to specific receptor systems showed it is an inducibly activated kinase, answering which upstream signals engage it.

    Evidence Co-IP and in vitro kinase assays with c-Kit/SCF, Lyn, and Vav associations with domain mapping

    PMID:7526158 PMID:7651724 PMID:7936643

    Open questions at the time
    • Order of kinase activation not yet resolved
    • Downstream substrates not defined
  3. 1996 High

    Resolving the directionality of the TEC–Lyn relationship placed TEC downstream of a Src-family kinase, clarifying activation hierarchy.

    Evidence In vitro phosphorylation, yeast two-hybrid, and fibroblast co-expression showing Lyn phosphorylates and activates TEC unidirectionally

    PMID:8621063

    Open questions at the time
    • Physiological receptor context of Lyn-TEC activation not fully defined
  4. 1998 High

    Identifying the PI3K-PtdIns(3,4,5)P3/PH-domain axis and PLCγ output defined the core membrane-recruitment and effector mechanism of TEC.

    Evidence Phospholipid binding, PLCγ phosphorylation, IP3 measurement, and SHIP inhibition in cell-based assays

    PMID:9524119

    Open questions at the time
    • Precise activation-loop phosphorylation events not mapped here
    • Receptor-specific contributions of PI3K not dissected
  5. 1999 High

    Distinguishing TEC from Itk in T cells answered whether Tec-family members have non-redundant effector functions, revealing a CD28-specific signaling role.

    Evidence Co-IP with SH3-domain specificity, in vitro phosphorylation of p62dok, and IL-2 reporter gain/loss-of-function in T cells

    PMID:10382746 PMID:9872994

    Open questions at the time
    • In vivo T-cell phenotype of TEC alone not established
    • Endogenous CD28-TEC stoichiometry unknown
  6. 1999 High

    Identifying BRDG1 as a TEC-selective substrate revealed a positive feedback docking protein that amplifies TEC activity in BCR signaling.

    Evidence Yeast two-hybrid, in vitro and in-cell phosphorylation with kinase-specificity comparison, and BCR stimulation

    PMID:10518561

    Open questions at the time
    • Structural basis of feedback amplification not resolved
    • In vivo requirement of BRDG1 not tested
  7. 2000 High

    Genetic and biochemical work defined TEC substrates and an essential Btk-redundant role, answering whether TEC matters at the organismal level.

    Evidence Btk/Tec double-knockout B cell developmental analysis plus Dok-1 complex/phosphorylation studies downstream of c-Kit

    PMID:11071635 PMID:11104803

    Open questions at the time
    • Mechanism of TEC/Btk functional overlap at molecular level not detailed
    • Whether unique TEC substrates contribute in vivo unclear
  8. 2001 High

    NMR structure of the SH3 domain and effector identification clarified autoinhibitory/dimerization control and extended the TEC substrate repertoire.

    Evidence NMR solution structure with mutagenesis defining intramolecular vs dimerization PRR-SH3 sites, plus identification of Sak as a TEC substrate

    PMID:11489907 PMID:11684687

    Open questions at the time
    • Cellular relevance of TEC dimerization not established
    • Physiological Sak-TEC pathway context unknown
  9. 2004 High

    Defining a unique adapter-independent route to NFAT and the PKCθ feedback loop established how TEC effector function diverges from other Tec-family kinases, while SHIP/Dok work mapped negative regulation.

    Evidence Reporter assays comparing family members, PKCθ co-IP with PH-domain requirement, and SHIP1/2 and Dok-1/2 inhibition assays

    PMID:14647425 PMID:14993283 PMID:15214048 PMID:15492005

    Open questions at the time
    • Identity of TEC's unique subcellular compartment not molecularly defined
    • Quantitative balance of positive vs negative regulators in vivo unclear
  10. 2010 High

    Defining the extended regulatory spine and SH2-kinase linker allostery explained how regulatory domains control catalysis, answering the structural logic of TEC activation.

    Evidence In vitro kinase assays with linker and spine mutations, gatekeeper mutation analysis, HDX-MS, and MD simulations (studied across Tec family)

    PMID:17425330 PMID:20826165 PMID:23982207 PMID:27010561

    Open questions at the time
    • Several mechanistic studies use Itk/Btk as model and generalize to TEC
    • Full-length autoinhibited TEC structure not solved
  11. 2008 High

    Genetic and biochemical work in osteoclasts, phagocytes, and antifungal immunity expanded TEC's role beyond lymphocytes to innate immunity and bone homeostasis.

    Evidence Btk/Tec double-KO osteopetrosis with RANK/ITAM/BLNK complex co-IP, Fcγ-receptor phagocytosis siRNA/inhibitor imaging, and Dectin-1/Syk-dependent caspase-8 inflammasome in fungal infection models

    PMID:18329366 PMID:18566394 PMID:25474208

    Open questions at the time
    • TEC-specific (vs Btk) contributions in some innate settings not separated
    • Direct TEC substrates in the caspase-8 inflammasome not identified
  12. 2016 High

    Identifying FGF2 as a direct TEC substrate during unconventional secretion revealed a function outside classical receptor-signaling pathways.

    Evidence In vitro kinase assay, co-IP, substrate-specific small-molecule inhibitors, and unconventional secretion assays

    PMID:27382052

    Open questions at the time
    • Physiological/in vivo significance of TEC in FGF2 export not established
    • Regulation of this non-canonical TEC pool unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • How TEC achieves substrate selectivity and unique subcellular targeting distinct from Btk and Itk in vivo, and whether its non-canonical roles (FGF2 secretion, caspase-8 inflammasome) have dedicated regulation, remain unresolved.
  • No full-length structure of autoinhibited or active TEC
  • TEC-specific in vivo loss-of-function phenotype (without Btk) not deeply characterized
  • Mechanism directing TEC to its unique compartment unknown

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:0008289 lipid binding 2 GO:0098772 molecular function regulator activity 2
Localization
GO:0005886 plasma membrane 3 GO:0005829 cytosol 1 GO:0005856 cytoskeleton 1
Pathway
R-HSA-168256 Immune System 5 R-HSA-109582 Hemostasis 3 R-HSA-162582 Signal Transduction 3 R-HSA-1266738 Developmental Biology 2
Partners
BTKDOK1INPP5DKITLYNPRKCQSOCS1VAV1
Complex memberships
RANK/ITAM/BLNK(SLP-76) osteoclastogenic complexnoncanonical caspase-8 inflammasome

Evidence

Reading pass · 38 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 C-terminal domain homology to Src family members, representing the founding member of what became the Tec kinase family. cDNA library screening with v-fps kinase domain probe; Northern blot analysis; sequence analysis Oncogene Medium 2284097
1994 Tec physically associates with c-kit through a proline-rich motif N-terminal to the SH3 domain; following stem cell factor (SCF) binding, Tec is tyrosine phosphorylated and its in vitro kinase activity is increased. This activation is SCF-specific and not induced by CSF-1, GM-CSF, or IL-3. Co-immunoprecipitation; in vitro kinase assay; tyrosine phosphorylation assay Molecular and cellular biology High 7526158
1994 Tec directly associates with Lyn protein-tyrosine kinase through the N-terminal unique domain (NTec2 region) of Tec; Lyn binds via its SH3 domain; the p56 form of Lyn is inducibly tyrosine-phosphorylated in response to IL-3 within this complex. GST-fusion pull-down; in vivo co-immunoprecipitation; in vitro binding assay Oncogene High 7936643
1994 The Tec homology (TH) domain adjacent to the PH domain contains a conserved ~27 amino acid Btk motif and a proline-rich region, defining it as a distinct structural element within Tec family kinases likely involved in protein-protein interactions. Sequence analysis; domain structure characterization FEBS letters Low 8070576
1995 Tec kinase associates with Vav upon erythropoietin and IL-3 stimulation; this interaction occurs through the Tec homology domain of Tec. Tec kinase is transiently activated by these cytokines, and Grb2 constitutively associates with Vav. Co-immunoprecipitation; in vitro binding assay; kinase activity assay Oncogene High 7651724
1995 Tec and Btk associate with gp130 (the shared signal transducer of IL-6 family cytokines) without ligand stimulation; IL-6 stimulation activates both Btk and Tec, while IL-3 and G-CSF activate Tec but not Btk in a pro-B cell line. Co-immunoprecipitation; kinase activation assay Blood High 7530500
1995 Tec is tyrosine phosphorylated and its kinase activity is activated following IL-3 stimulation in myeloid and pro-B cell lines; Tec constitutively associates with the Shc adapter protein in vivo. Anti-Tec immunoprecipitation; in vitro kinase assay; co-immunoprecipitation Blood Medium 7811991
1996 Lyn kinase directly phosphorylates tyrosine residues of Tec and thereby activates Tec, while Tec co-expression has little effect on Lyn phosphotyrosine content, establishing that Tec acts downstream of Lyn. Demonstrated both in vitro and in a yeast system. In vitro kinase assay; yeast two-hybrid system; co-expression in 3T3 fibroblasts FASEB journal High 8621063
1996 Tec is tyrosine phosphorylated and activated by G-CSF stimulation in both cell growth and differentiation contexts; Vav associates with Tec and is tyrosine phosphorylated in response to G-CSF. Immunoprecipitation; kinase activity assay; co-immunoprecipitation Cell growth & differentiation Medium 8877094
1997 SOCS-1/JAB/SSI-1 (identified as TIP3) associates with Tec in 293 cells and suppresses its kinase activity, while also down-regulating Jak2 but not Lyn activity, identifying SOCS-1 as a negative regulator of Tec. Yeast two-hybrid screening; co-immunoprecipitation in 293 cells; kinase activity assay The Journal of biological chemistry High 9341160
1997 JAK1 (but not JAK2) associates with Tec and Btk; JAK1 induces tyrosine phosphorylation of Btk but not Tec. Tec interacts with p85 and p55PIK subunits of PI-3 kinase (dependent on Tec kinase activity) and with Vav (via SH2 domain, independent of kinase activity). IL-6 and IL-3 induce Tec-p85 PI3K association in mammalian cells. Co-immunoprecipitation; yeast two-hybrid; overexpression in mammalian cells Oncogene High 9178903
1998 PtdIns-3,4,5-P3 interacting with the Tec PH domain acts as an upstream activation signal for Tec kinases, resulting in Tec kinase-dependent PLCγ tyrosine phosphorylation and IP3 production. The SHIP inositol phosphatase blocks this pathway by degrading PtdIns-3,4,5-P3. Cell-based signaling assays; phospholipid binding; PLCγ phosphorylation assay; IP3 production measurement The EMBO journal High 9524119
1998 Tec and Bmx activate serum response factor (SRF) in synergy with constitutively active Gα12/13 subunits; this SRF activation is Rho-dependent (blocked by C3 transferase). The kinase and Tec homology domains are required. Gα12 and Gα13 stimulate Tec autophosphorylation and transphosphorylation activities. Transient transfection; SRF reporter assay; C3 transferase inhibition; kinase activity assay; domain deletion analysis The EMBO journal High 9755164
1998 Tec is rapidly tyrosine phosphorylated in human platelets in response to G protein-coupled receptor agonists (thromboxane A2 analog, thrombin, TRAP) and integrin engagement (adhesion to fibrinogen or collagen). Tec translocates to the cytoskeleton upon TRAP stimulation in a manner dependent on platelet aggregation, indicating a role in integrin-mediated signaling. Immunoprecipitation; tyrosine phosphorylation assay; subcellular fractionation; platelet activation assays Oncogene Medium 9652744
1998 Tec is expressed throughout human B cell differentiation and can be activated by BCR cross-linking (inducing tyrosine phosphorylation and increased kinase activity) and CD19 or CD38 ligation; Tec responds to CD38 stimulation whereas Btk does not, indicating differential regulation. Immunoprecipitation; in vitro kinase assay; anti-receptor antibody stimulation Blood Medium 9446655
1999 Tec is activated following TCR/CD3 or CD28 ligation in T cells. Tec interacts with CD28 in an activation-dependent manner via the Tec SH3 domain binding to proline-rich motifs in CD28. Tec phosphorylates p62dok, a CD28-specific substrate (unlike Itk). Overexpression of Tec (but not Itk) enhances IL-2 promoter activity following TCR/CD3 or CD28 stimulation. Co-immunoprecipitation; in vitro kinase assay; luciferase reporter assay; dominant-negative overexpression The Journal of biological chemistry High 9872994
1999 Tec kinase is involved in IL-2 and IL-4 transcriptional regulation downstream of CD28; CD28-mediated Tec activation requires Src family PTK activity (Lck), as kinase-dead Lck blocks Tec activation and Tec-induced cytokine expression. Reporter assay (IL-2 and IL-4 promoter-luciferase); co-expression of kinase-dead mutants European journal of immunology Medium 10382746
1999 BRDG1 (BCR downstream signaling 1) was identified as a downstream docking protein of Tec. Tec (but not Btk, Bmx, Lyn, Syk, or c-Abl) phosphorylates BRDG1 on tyrosine in cells and directly in vitro. Efficient phosphorylation requires PH and SH2 domains plus the kinase domain of Tec. BRDG1 participates in a positive feedback loop increasing Tec activity, and undergoes tyrosine phosphorylation in response to BCR stimulation. Yeast two-hybrid; in vitro kinase assay; in vivo phosphorylation in 293 cells; BCR stimulation assay Proceedings of the National Academy of Sciences of the United States of America High 10518561
2000 SCF/cKit signaling leads to PI3K-dependent activation and phosphorylation of Tec and Dok-1, which form a stable complex with Lyn and two unidentified phosphoproteins. The Tec homology domain and SH2 domain of Tec are required for interaction with Dok-1. Tec and Lyn phosphorylate Dok-1, which then binds SH2 domains of Abl, CrkL, SHIP, and PLCγ-1. Co-immunoprecipitation; in vitro kinase assay; PI3K inhibitor studies; domain deletion analysis Blood High 11071635
2000 Tec/Btk double-deficient mice exhibit a block at the B220+CD43+ stage of B cell development and severe reduction of peripheral B cells (particularly IgMloIgDhi), demonstrating that Tec and Btk together have an essential non-redundant role in B cell development that neither alone is required for. Genetic knockout; B cell developmental analysis by flow cytometry; immunological phenotyping The Journal of experimental medicine High 11104803
2000 Both Btk and Tec undergo rapid tyrosine phosphorylation in platelets following stimulation of the GPVI collagen receptor or CD32 cross-linking, with coordinate recruitment through ITAM, Src family kinases, and PI3K. In XLA platelets lacking Btk, Tec phosphorylation is preserved along with downstream signaling molecules. Immunoprecipitation; phosphopeptide-specific antibodies; kinase inhibitor studies; platelet stimulation assays Blood Medium 10688822
2001 The solution NMR structure of the Tec SH3 domain was determined; the Tec proline-rich region (PRR) can bind intramolecularly to the SH3 domain (site 1: 155KTLPPAP161 binds intramolecularly; site 2: 165KRRPPPPIPP174 binds intermolecularly/dimerization). The affinity for dimerization via reciprocal PRR-SH3 is higher than for the intramolecular interaction. NMR solution structure determination; site-directed mutagenesis; binding affinity measurements The Journal of biological chemistry High 11684687
2001 Sak serine-threonine kinase (a Polo-family member) is phosphorylated on tyrosine by Tec in 293 cells and directly in vitro; Tec activates the serine-threonine kinase activity of Sak and protects it from PEST sequence-dependent proteolysis, establishing Sak as an effector molecule of Tec. Yeast two-hybrid; in vitro kinase assay; co-expression in 293 cells; proteolysis assay The Journal of biological chemistry High 11489907
2003 Tec plays a role in platelet activation by GPVI in the absence of Btk. Btk/Tec double-deficient platelets fail to undergo Ca2+ increase, aggregation, secretion, and spreading in response to collagen or CRP, whereas Tec-/- alone shows only minor reduction. PLCγ2 tyrosine phosphorylation is further reduced in Btk/Tec double-deficient compared to Btk-/- platelets. Genetic knockout (single and double KO); platelet aggregation assay; calcium measurement; PLCγ2 phosphorylation assay Blood High 12842985
2003 TGF-β inhibits Tec kinase (Itk) phosphorylation and activation in stimulated CD4+ T cells, leading to reduced Ca2+ influx, impaired NFATc translocation, and reduced ERK activation, thereby blocking T cell differentiation at a proximal signaling step. Kinase phosphorylation assay; calcium influx measurement; NFATc translocation assay; ERK activation assay The Journal of experimental medicine Medium 12810687
2004 Tec overexpression in lymphocyte cell lines induces PLCγ phosphorylation and NFAT activation, whereas overexpression of Btk, Itk, or Bmx does not induce NFAT activation. Tec-induced NFAT activation requires PLCγ but not the adapters LAT, SLP-76, and BLNK (which are required for Btk and Itk). Tec has a unique subcellular localization correlating with this distinct effector function. Overexpression in cell lines; NFAT reporter assay; PLCγ phosphorylation; subcellular localization Molecular and cellular biology Medium 14993283
2004 PKCθ constitutively associates with Tec (interaction requires the Tec PH domain). Wild-type Tec (but not Itk or Rlk) potently activates AP-1 downstream of PKCθ, and dominant-negative Tec blocks PKCθ-induced AP-1 (but not NF-κB) activation. Tec thus mediates a PKCθ→Tec→PLCγ1→Ca2+ positive feedback loop regulating AP-1 in restimulated T cells. Co-immunoprecipitation; reporter assay (AP-1, NF-κB); dominant-negative overexpression; calcium measurement European journal of immunology Medium 15214048
2004 SHIP1 and SHIP2 interact preferentially with Tec (via its SH3 domain) compared to other Tec family members, and function as negative regulators: they inhibit Tec activity, and SHIP1 inhibits Tec membrane localization. Inactivation of the Tec SH3 domain generates a hyperactive Tec. Constitutive membrane targeting of Tec relieves SHIP1-mediated inhibition. Co-immunoprecipitation; kinase activity assay; subcellular fractionation; constitutively membrane-targeted mutant; SH3 domain mutant analysis The Journal of biological chemistry High 15492005
2004 Dok-1 and Dok-2 are major tyrosine-phosphorylated proteins associated with Tec in T cells and act as negative feedback regulators of Tec, downregulating its tyrosine phosphorylation and downstream Ras pathway signaling. Co-immunoprecipitation; tyrosine phosphorylation assay; Ras pathway reporter assay Oncogene Medium 14647425
2004 Tec PH domain is required for Tec-mediated IL-2 gene induction and TCR-mediated Tec tyrosine phosphorylation in T cells. Tec colocalizes with the TCR after cross-linking (both PH and SH2 domains involved). Wortmannin (PI3K inhibitor) abolishes Tec phosphorylation and IL-2 induction, establishing PI3K-PH domain signaling axis upstream of Tec. PH domain mutant overexpression; IL-2 reporter assay; tyrosine phosphorylation assay; confocal microscopy; wortmannin inhibition Journal of immunology Medium 11123316
2007 The short linker region between the SH2 and kinase domains of Tec family kinases (studied via Itk as model) positively regulates catalytic activity. Precise conserved residues in this linker allosterically regulate activity, a mechanism conserved among Tec kinases but distinct from Src kinase regulation. Quantitative in vitro kinase assay; linker deletion/mutation analysis Biochemistry High 17425330
2008 Btk and Tec together regulate osteoclast differentiation downstream of RANK and ITAM signals. Mice lacking both Btk and Tec show severe osteopetrosis. RANK and ITAM signaling forms a Btk(Tec)/BLNK(SLP-76)-containing complex leading to PLCγ-mediated calcium signaling required for NFATc1 activation and osteoclastogenesis. Double-KO mouse model; osteoclast differentiation assay; co-immunoprecipitation of signaling complex; calcium measurement; Tec kinase inhibitor in disease models Cell High 18329366
2008 Btk and Tec are activated throughout FcγR-induced phagocytosis in macrophages, accumulating at the base of phagocytic cups. Their inhibition (by LFM-A13 or siRNA) significantly inhibits FcγR-induced phagocytosis. Btk and Tec regulate FcγR-induced Mac-1 activation required for optimal phagocytosis. A late/prolonged PLCγ2 activation (after initial Syk-dependent phase) is dependent on Btk and Tec. Activated Btk (but not Tec) co-localizes with phagosomal diacylglycerol. siRNA knockdown; pharmacological inhibition; live-cell imaging; subcellular fractionation; PLCγ2 phosphorylation assay; Mac-1 activation assay Journal of immunology High 18566394
2010 The extended regulatory spine within Tec kinases (identified via Itk/Btk) includes a conserved methionine in the C-helix and a conserved tryptophan in the SH2-kinase linker, forming an allosteric conduit from regulatory domains to the catalytic domain. Mutation of the gatekeeper residue stabilizes the regulatory spine, rendering a constitutively active kinase in which activation loop phosphorylation is unnecessary. In vitro kinase assay; mutagenesis; structural analysis of regulatory spine residues Journal of molecular biology High 20826165
2013 Btk and Itk (Tec family members) have distinct catalytic efficiencies due to differences in activation loop dynamics. Substitution of 6 residues in the activation segment of Itk with corresponding Btk residues (and vice versa) completely swaps their kinase activities. NMR and HDX-MS revealed distinct dynamics in the activation loop explaining the catalytic efficiency differences. In vitro kinase assay; mutagenesis (activation segment substitutions); NMR; hydrogen-deuterium exchange mass spectrometry; T cell TCR signaling assays Science signaling High 23982207
2014 Tec kinase is required for activation and assembly of the noncanonical caspase-8 inflammasome (but not the caspase-1 inflammasome) in macrophages during Candida albicans infection. Dectin-1 is the pathogen recognition receptor required for Syk-dependent Tec activation. Tec genetic ablation or small-molecule inhibition protects mice from fungal sepsis. Genetic knockout; small-molecule inhibition; in vivo fungal infection model; inflammasome assembly assay; IL-1β production assay PLoS pathogens High 25474208
2016 Tec kinase directly phosphorylates FGF2 on tyrosine to stimulate FGF2 membrane pore formation during unconventional secretion. Small molecules that inhibit FGF2-Tec interaction also inhibit FGF2 tyrosine phosphorylation in vitro and in cells, and block unconventional FGF2 secretion. Inhibitors are specific for FGF2 as a Tec substrate (tyrosine phosphorylation of a different Tec substrate is unaffected). In vitro kinase assay; co-immunoprecipitation; small-molecule inhibitor; unconventional secretion assay in cells; substrate specificity assay The Journal of biological chemistry High 27382052
2016 A conserved tryptophan in the SH2-kinase linker of Tec family kinases mediates allosteric activation of Btk; mutation to alanine abolishes activity. Specific tryptophan side chain rotamer promotes coordinated motions across the kinase domain. This dynamic allostery is conserved across the Tec family. HDX mass spectrometry; molecular dynamics simulations; principal component analysis; mutagenesis; kinase activity assay PLoS computational biology Medium 27010561

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 324 9524120
1999 Requirement for Tec kinases Rlk and Itk in T cell receptor signaling and immunity. Science (New York, N.Y.) 311 10213685
2005 Tec family kinases in T lymphocyte development and function. Annual review of immunology 273 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 238 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 214 20519342
2010 The Src, Syk, and Tec family kinases: distinct types of molecular switches. Cellular signalling 202 20206686
1994 BMX, a novel nonreceptor tyrosine kinase gene of the BTK/ITK/TEC/TXK family located in chromosome Xp22.2. Oncogene 171 7970727
2006 Altered development of CD8+ T cell lineages in mice deficient for the Tec kinases Itk and Rlk. Immunity 159 16860760
2000 Severe B cell deficiency in mice lacking the tec kinase family members Tec and Btk. The Journal of experimental medicine 155 11104803
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 151 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 136 15803148
2003 Tec regulates platelet activation by GPVI in the absence of Btk. Blood 136 12842985
2003 Transforming growth factor beta blocks Tec kinase phosphorylation, Ca2+ influx, and NFATc translocation causing inhibition of T cell differentiation. The Journal of experimental medicine 134 12810687
2019 PF-06651600, a Dual JAK3/TEC Family Kinase Inhibitor. ACS chemical biology 126 31082193
1999 Tec family of protein-tyrosine kinases: an overview of their structure and function. Cytokine & growth factor reviews 122 10647781
2007 Signalling through TEC kinases regulates conventional versus innate CD8(+) T-cell development. Nature reviews. Immunology 117 17479128
2008 Dual functions of Bruton's tyrosine kinase and Tec kinase during Fcgamma receptor-induced signaling and phagocytosis. Journal of immunology (Baltimore, Md. : 1950) 114 18566394
2009 Tec kinase Itk in gammadeltaT cells is pivotal for controlling IgE production in vivo. Proceedings of the National Academy of Sciences of the United States of America 113 19416854
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 103 11015440
1994 Tec homology (TH) adjacent to the PH domain. FEBS letters 98 8070576
2008 The tec family tyrosine kinase Btk Regulates RANKL-induced osteoclast maturation. The Journal of biological chemistry 95 18281276
1997 SOCS-1/JAB/SSI-1 can bind to and suppress Tec protein-tyrosine kinase. The Journal of biological chemistry 95 9341160
2008 The Tec kinases Itk and Rlk regulate NKT cell maturation, cytokine production, and survival. Journal of immunology (Baltimore, Md. : 1950) 94 18292523
1994 Tec kinase associates with c-kit and is tyrosine phosphorylated and activated following stem cell factor binding. Molecular and cellular biology 94 7526158
1995 Interleukin 3 and erythropoietin induce association of Vav with Tec kinase through Tec homology domain. Oncogene 89 7651724
1999 The role of Tec protein-tyrosine kinase in T cell signaling. The Journal of biological chemistry 87 9872994
2012 TCR signaling via Tec kinase ITK and interferon regulatory factor 4 (IRF4) regulates CD8+ T-cell differentiation. Proceedings of the National Academy of Sciences of the United States of America 83 23011795
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
2004 Requirement for Tec kinases in chemokine-induced migration and activation of Cdc42 and Rac. Current biology : CB 80 15186750
2002 Beyond calcium: new signaling pathways for Tec family kinases. Journal of cell science 80 12118060
1995 Tec protein-tyrosine kinase is involved in interleukin-3 signaling pathway. Blood 77 7811991
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
2004 Expression and function of Tec, Itk, and Btk in lymphocytes: evidence for a unique role for Tec. Molecular and cellular biology 73 14993283
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 71 10523612
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.) 69 32419304
2002 New insights into the regulation and functions of Tec family tyrosine kinases in the immune system. Current opinion in immunology 68 11973131
2003 The role of Tec family kinases in T cell development and function. Immunological reviews 66 12614356
2009 The Tec kinases Itk and Rlk regulate conventional versus innate T-cell development. Immunological reviews 64 19290924
2004 Regulation of CXC chemokine receptor 4-mediated migration by the Tec family tyrosine kinase ITK. The Journal of biological chemistry 64 15123627
2011 Tec family kinases Itk and Rlk / Txk in T lymphocytes: cross-regulation of cytokine production and T-cell fates. The FEBS journal 63 21362139
2012 Tec family kinases in inflammation and disease. International reviews of immunology 61 22449071
1993 Elimination of Tec elements involves a novel excision process. Genes & development 60 8380782
1998 Expression and activation of the nonreceptor tyrosine kinase Tec in human B cells. Blood 59 9446655
2005 Regulation of highly cytokinergic IgE-induced mast cell adhesion by Src, Syk, Tec, and protein kinase C family kinases. Journal of immunology (Baltimore, Md. : 1950) 57 15814670
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 56 15214048
2001 Tec kinase signaling in T cells is regulated by phosphatidylinositol 3-kinase and the Tec pleckstrin homology domain. Journal of immunology (Baltimore, Md. : 1950) 53 11123316
2007 Tec kinases in T cell and mast cell signaling. Advances in immunology 52 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
1999 A role for the Tec family tyrosine kinase Txk in T cell activation and thymocyte selection. The Journal of experimental medicine 48 10562318
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 46 38263353
1996 Tec protein-tyrosine kinase is an effector molecule of Lyn protein-tyrosine kinase. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 44 8621063
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
1994 Molecular cloning and analysis of the human Tec protein-tyrosine kinase. Leukemia 42 7934162
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
2021 Hierarchy of signaling thresholds downstream of the T cell receptor and the Tec kinase ITK. Proceedings of the National Academy of Sciences of the United States of America 40 34452995
2011 Tec family kinases: regulation of FcεRI-mediated mast-cell activation. The FEBS journal 40 21362140
2006 Tec kinases Itk and Rlk are required for CD8+ T cell responses to virus infection independent of their role in CD4+ T cell help. Journal of immunology (Baltimore, Md. : 1950) 40 16424186
2005 Tec kinases regulate TCR-mediated recruitment of signaling molecules and integrin-dependent cell adhesion. Journal of immunology (Baltimore, Md. : 1950) 40 16237085
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 39 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
2014 The non-receptor tyrosine kinase Tec controls assembly and activity of the noncanonical caspase-8 inflammasome. PLoS pathogens 35 25474208
2011 TEC family kinases in health and disease--loss-of-function of BTK and ITK and the gain-of-function fusions ITK-SYK and BTK-SYK. The FEBS journal 35 21518255
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
1994 Tec protein-tyrosine kinase directly associates with Lyn protein-tyrosine kinase through its N-terminal unique domain. Oncogene 35 7936643
2023 Improvements in immune/melanocyte biomarkers with JAK3/TEC family kinase inhibitor ritlecitinib in vitiligo. The Journal of allergy and clinical immunology 33 37777018
2015 Adult thymic epithelial cell (TEC) progenitors and TEC stem cells: Models and mechanisms for TEC development and maintenance. European journal of immunology 33 26362014
2010 Identification of an allosteric signaling network within Tec family kinases. Journal of molecular biology 33 20826165
1999 Tec kinase is involved in transcriptional regulation of IL-2 and IL-4 in the CD28 pathway. European journal of immunology 32 10382746
1998 Tec is involved in G protein-coupled receptor- and integrin-mediated signalings in human blood platelets. Oncogene 32 9652744
2022 The monomer TEC of blueberry improves NASH by augmenting tRF-47-mediated autophagy/pyroptosis signaling pathway. Journal of translational medicine 31 35287671
2004 Functional interaction of RasGAP-binding proteins Dok-1 and Dok-2 with the Tec protein tyrosine kinase. Oncogene 31 14647425
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
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
2018 Multidomain Control Over TEC Kinase Activation State Tunes the T Cell Response. Annual review of immunology 28 29677469
2008 The Tec family kinase, IL-2-inducible T cell kinase, differentially controls mast cell responses. Journal of immunology (Baltimore, Md. : 1950) 28 18523250
1996 Tec protein tyrosine kinase is involved in the signaling mechanism of granulocyte colony-stimulating factor receptor. Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research 28 8877094
2013 Activation loop dynamics determine the different catalytic efficiencies of B cell- and T cell-specific tec kinases. Science signaling 27 23982207
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
2006 Tec kinase Itk forms membrane clusters specifically in the vicinity of recruiting receptors. The Journal of biological chemistry 27 17060314
2011 Tec family kinases: Itk signaling and the development of NKT αβ and γδ T cells. The FEBS journal 26 21362141

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