TNS3
Description
The TNS3 (tensin 3) is a protein-coding gene located on chromosome 7.
Tensin-3, also known as Tensin-like SH2 domain-containing protein 1, Tumor endothelial marker 6. May act as a protein phosphatase and/or a lipid phosphatase (Probable). Involved in the dissociation of the integrin-tensin-actin complex (PubMed:17643115). EGF activates TNS4 and down-regulates TNS3 which results in capping the tail of ITGB1 (PubMed:17643115). Increases DOCK5 guanine nucleotide exchange activity towards Rac and plays a role in osteoclast podosome organization (By similarity). Enhances RHOA activation in the presence of DLC1 (PubMed:26427649). Required for growth factor-induced epithelial cell migration; growth factor stimulation induces TNS3 phosphorylation which changes its binding preference from DLC1 to the p85 regulatory subunit of the PI3K kinase complex, displacing PI3K inhibitor PTEN and resulting in translocation of the TNS3-p85 complex to the leading edge of migrating cells to promote RAC1 activation (PubMed:26166433). Meanwhile, PTEN switches binding preference from p85 to DLC1 and the PTEN-DLC1 complex translocates to the posterior of migrating cells to activate RHOA (PubMed:26166433). Acts as an adapter protein by bridging the association of scaffolding protein PEAK1 with integrins ITGB1, ITGB3 and ITGB5 which contributes to the promotion of cell migration (PubMed:35687021). Controls tonsil-derived mesenchymal stem cell proliferation and differentiation by regulating the activity of integrin ITGB1 (PubMed:31905841). Interacts with EGFR; EGF promotes the interaction with EGFR (PubMed:15140944). Interacts with PTK2/FAK1 and BCAR1 (PubMed:15140944). Tyrosine phosphorylation is critical for these interactions (PubMed:15140944). Interacts with Rho GTPase-activating protein DLC1 and with the regulatory p85 subunit of the PI3K kinase complex; in resting cells, interacts (via C2 tensin-type domain) with DLC1 but, following growth factor stimulation, TNS3 is phosphorylated which leads to weakened interaction with DLC1 and enhanced interaction (via C2 tensin-type domain) with p85 while DLC1 interaction with PTEN increases (PubMed:26166433). Interacts (when phosphorylated on the SH2 domain) with integrins ITGB1, ITGB3 and ITGB5 and with scaffolding protein PEAK1 (phosphorylated on 'Tyr-635'); mediates the association of PEAK1 with ITGB1, ITGB3 and ITGB5 (PubMed:35687021). Interacts (via N-terminus) with DOCK5 (via N-terminus); the interaction increases DOCK5 guanine nucleotide exchange activity towards Rac (By similarity). Interacts with receptor tyrosine kinase MET (PubMed:24814316).
TNS3, also known as Tensin-like SH2 domain-containing protein 1, Tumor endothelial marker 6, might function as a protein phosphatase or a lipid phosphatase. It is involved in the separation of the integrin-tensin-actin complex. EGF activates TNS4 and downregulates TNS3, resulting in the capping of the ITGB1 tail. TNS3 enhances DOCK5 guanine nucleotide exchange activity toward Rac and plays a role in osteoclast podosome organization. It also increases RHOA activation in the presence of DLC1. TNS3 is essential for growth factor-induced epithelial cell migration, where growth factor stimulation causes phosphorylation of TNS3. This alters its binding preference from DLC1 to the p85 regulatory subunit of the PI3K kinase complex, displacing the PI3K inhibitor PTEN. As a result, the TNS3-p85 complex translocates to the leading edge of migrating cells, promoting RAC1 activation. Concurrently, PTEN switches its binding preference from p85 to DLC1, and the PTEN-DLC1 complex translocates to the posterior of migrating cells, activating RHOA. TNS3 acts as an adapter protein, connecting the scaffolding protein PEAK1 with integrins ITGB1, ITGB3, and ITGB5, which contributes to cell migration. TNS3 controls the proliferation and differentiation of tonsil-derived mesenchymal stem cells by regulating the activity of integrin ITGB1.
TNS3 is also known as TEM6, TENS1.
