Tyrosine-protein kinase Tec

Function

Non-receptor tyrosine kinase that contributes to signaling from many receptors and participates as a signal transducer in multiple downstream pathways, including regulation of the actin cytoskeleton. Plays a redundant role to ITK in regulation of the adaptive immune response. Regulates the development, function and differentiation of conventional T-cells and nonconventional NKT-cells. Required for TCR-dependent IL2 gene induction. Phosphorylates DOK1, one CD28-specific substrate, and contributes to CD28-signaling. Mediates signals that negatively regulate IL2RA expression induced by TCR cross-linking. Plays a redundant role to BTK in BCR-signaling for B-cell development and activation, especially by phosphorylating STAP1, a BCR-signaling protein. Required in mast cells for efficient cytokine production. Involved in both growth and differentiation mechanisms of myeloid cells through activation by the granulocyte colony-stimulating factor CSF3, a critical cytokine to promoting the growth, differentiation, and functional activation of myeloid cells. Participates in platelet signaling downstream of integrin activation. Cooperates with JAK2 through reciprocal phosphorylation to mediate cytokine-driven activation of FOS transcription. GRB10, a negative modifier of the FOS activation pathway, is another substrate of TEC. TEC is involved in G protein-coupled receptor- and integrin-mediated signalings in blood platelets. Plays a role in hepatocyte proliferation and liver regeneration and is involved in HGF-induced ERK signaling pathway. TEC also regulates FGF2 unconventional secretion (endoplasmic reticulum (ER)/Golgi-independent mechanism) under various physiological conditions through phosphorylation of FGF2 'Tyr-215'. May also be involved in the regulation of osteoclast differentiation.

Classification

Family (Pfam)

PF00779 BTK, PF00169 PH, PF07714 PK_Tyr_Ser-Thr, PF00017 SH2, PF00018 SH3_1

InterPro

Kinase-like_dom_sf, Non-receptor_tyrosine_kinases, PH-like_dom_sf, PH_domain, Prot_kinase_dom, Protein_kinase_ATP_BS, Ser-Thr/Tyr_kinase_cat_dom, SH2, SH2_dom_sf, SH3-like_dom_sf, SH3_domain, Tec_SH3, Tyr_kinase_AS, Tyr_kinase_cat_dom, Znf_Btk_motif

Functional cluster

Serine/Threonine Protein Kinases

Experimental structures · PDB · 1

• 2LUL NMR

A predicted model is available from AlphaFold.

Gene Ontology · 14

• GO:0005856 cytoskeleton
• GO:0005829 cytosol
• GO:0005886 plasma membrane
• GO:0005524 ATP binding
• GO:0004715 non-membrane spanning protein tyrosine kinase activity
• GO:0005543 phospholipid binding
• GO:0008270 zinc ion binding
• GO:0002250 adaptive immune response
• GO:0050853 B cell receptor signaling pathway
• GO:0007229 integrin-mediated signaling pathway
• GO:0035556 intracellular signal transduction
• GO:0006468 protein phosphorylation
• GO:0010543 regulation of platelet activation
• GO:0050852 T cell receptor signaling pathway

Drugs targeting this protein · 2

• RITLECITINIB inhibitor
• RITLECITINIB TOSYLATE inhibitor

Related proteins · sequence + function similarity

• Tyrosine-protein kinase Tec 0.99
• Tyrosine-protein kinase BTK 0.95
• Tyrosine-protein kinase BTK 0.95
• Tyrosine-protein kinase BTK 0.95
• Tyrosine-protein kinase ITK/TSK 0.95
• Tyrosine-protein kinase ITK/TSK 0.92
• Tyrosine-protein kinase TXK 0.91
• Cytoplasmic tyrosine-protein kinase BMX 0.89
• Tyrosine-protein kinase transforming protein Abl 0.88
• Tyrosine-protein kinase CSK 0.88
• Tyrosine-protein kinase HCK 0.88
• Tyrosine-protein kinase Lyn 0.87

Co-cited proteins · studied together in the literature

• Signal-transducing adaptor protein 1 1 shared papers
• Growth factor receptor-bound protein 10 1 shared papers
• Suppressor of cytokine signaling 1 1 shared papers
• Fibroblast growth factor 2 1 shared papers
• Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2 1 shared papers
• Tyrosine-protein kinase ITK/TSK 1 shared papers
• Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1 1 shared papers
• Cytoplasmic tyrosine-protein kinase BMX 1 shared papers
• Tyrosine-protein kinase BTK 1 shared papers

Literature · 16 cited papers

• Tec-kinase-mediated phosphorylation of fibroblast growth factor 2 is essential for unconventional secretion. Traffic · 2010
• Tec protein tyrosine kinase inhibits CD25 expression in human T-lymphocyte. Immunol. Lett. · 2010
• Identification of SH3 domain interaction partners of human FasL (CD178) by phage display screening. BMC Immunol. · 2009
• Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci. Signal. · 2009
• Large-scale proteomics analysis of the human kinome. Mol. Cell. Proteomics · 2009
• Patterns of somatic mutation in human cancer genomes. Nature · 2007
• SHIP family inositol phosphatases interact with and negatively regulate the Tec tyrosine kinase. J. Biol. Chem. · 2004
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
• Identification of phosphorylation sites within the SH3 domains of Tec family tyrosine kinases. Biochim. Biophys. Acta · 2003
• Molecular cloning of a docking protein, BRDG1, that acts downstream of the Tec tyrosine kinase. Proc. Natl. Acad. Sci. U.S.A. · 1999
• Grb10/GrbIR as an in vivo substrate of Tec tyrosine kinase. Genes Cells · 1998
• Tec is involved in G protein-coupled receptor- and integrin-mediated signalings in human blood platelets. Oncogene · 1998
• … and 4 more in the literature graph