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TEC (gene)

Tyrosine-protein kinase Tec is a tyrosine kinase that in humans is encoded by the TEC gene. Tec kinase is expressed in hematopoietic, liver, and kidney cells and plays an important role in T-helper cell processes. Tec kinase is the name-giving member of the Tec kinase family, a family of non-receptor protein-tyrosine kinases.

Structure
Tec kinase contains five protein interaction domains. The characteristic feature of Tec family kinases is a pleckstrin homology (PH) domain on the N-terminus of the molecule followed by a Tec homology (TH) domain. The TH domain of Tec kinase contains a Btk homology (BH) motif and two proline-rich (PR) regions. The other protein interaction domains of Tec kinase include Src homology (SH) domains SH2 and SH3 and a kinase domain with enzymatic activity. TEC produces two protein isoforms that differ in the SH3 domain through alternative splicing. Type IV isoform has a full length SH3 domain and is predominately expressed in hematopoietic cells. Type III isoform has a SH3 domain that lacks the COOH-terminal 22 residues and is predominately expressed in the liver and kidney. It is likely the shortened SH3 domain of type III Tec kinase is a disabled form. TEC resides on chromosome 4, locus 4p12 in humans. TEC is located only 1.5kb away from TXK, another member of the Tec kinase family, making it likely these two kinase genes arose through the process of gene-duplication. == Function ==
Function
Functions of Tec family kinases Tec family kinases are involved in the intracellular signaling mechanisms of cytokine receptors, lymphocyte surface antigens, heterotrimeric G-protein-coupled receptors, and integrin molecules. They are also key players in the regulation of the immune functions. Functions of Tec kinase Lymphoid Cells Tec kinase has low expression in naïve T cells but is upregulated upon T-cell activation, especially in the presence of TGF-ß1 and IL-6. Myeloid Cells Tec kinase plays a role in the toll-like receptor (TLR) signaling pathway of macrophages that produces pro-inflammatory cytokines TNF-α and IL-6. Btk has an important function in this pathway, as it has been observed to bind to TLR4, MyD88, and IRAK-1 signaling proteins. Tec kinase is likely involved in the same manner in macrophages, as it has a compensatory function for Btk. Tec kinase is activated in platelets upon platelet stimulation with thrombin or collagen. Tec kinase is involved in the regulation of PLCγ2 activation, platelet aggregation, and spreading GPVI collagen receptor. Btk plays a more important role in these processes, but Tec kinase is able to compensate for loss of Btk in XLA immune-deficient patients. Patients deficient in both Btk and Tec kinase display greatly impaired phosphorylation of PLCγ2, no aggregation of platelets in response to high doses of collagen, and greatly impaired spreading of collagen. Tec kinase is activated in neutrophils upon neutrophil stimulation with chemoattractant fMLP. It is not clear what the function of Tec kinase is in neutrophils. Tec kinase is also expressed in primary mast cells and erythroid cells. Its function has not been identified in these cells. == Activation ==
Activation
Tec kinase is activated through a similar process to other members of the Tec kinase family. Tec kinase must first be relocated to the plasma membrane, which is mediated by the interaction of its PH domain with phospholipid PIP3 generated from PI3-K activity. A tyrosine residue within the kinase domain of Tec kinase is then phosphorylated by Src family kinases. This allows for autophosphorylation of a tyrosine residue in the Tec kinase SH3 domain, which allows the Tec kinase to be fully activated. == Clinical Significance ==
Clinical Significance
Rheumatoid arthritis (RA) is an autoimmune disorder that results in swollen, painful joints. Standard treatment for RA involves recombinant antibodies and receptors, but this biological therapy is costly. Inhibition of Tec family kinases may provide an alternative treatment for RA. Btk is the main target of inhibition, but because of the compensatory role of Tec kinase to Btk, an inhibition involving both Btk and Tec kinase may be needed. Blocking Tec family kinases could reduce the production of autoantibodies from B cells, limit the secretion of proinflammatory cytokines from macrophages, and inhibit mast cell degranulation. == Discovery ==
Discovery
Tec kinase was first discovered in 1990 while researchers investigated mouse liver for novel protein-tyrosine kinase isolation. Expression of Tec kinase was initially found in mouse liver, kidney, spleen, and heart. == Interactions ==
Interactions
TEC (gene) has been shown to interact with: • ARHGEF12, • DOK1, • GNA12, • Janus kinase 2, and • Suppressor of cytokine signaling 1. == References ==
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