Disease relevance of Tns1

• Mice with overt signs of weakness exhibited signs of renal failure and possessed multiple large cysts in the proximal kidney tubules, but even in tensin null mice with normal blood analysis, cysts were prevalent [1].
• Pten (phosphatase and tensin homologue gene) haploinsufficiency promotes insulin hypersensitivity [2].
• In mice, widespread deletion of the tumor suppressor Phosphatase and tensin homolog (PTEN) generates hamartomatous intestinal polyps with epithelial and stromal involvement [3].
• Focusing on a candidate transcript that has not been previously linked to hypertrophy, we found that protein levels of the tumor suppressor PTEN (phosphatase and tensin homologue on chromosome ten) were increased in the absence of increased messenger RNA levels [4].
• Mutations of the 'phosphatase and tensin homologue deleted on chromosome 10' (PTEN/MMAC1) gene have been associated with a variety of human cancers, including prostate cancer, glioblastoma, and melanoma [5].

High impact information on Tns1

• PTEN is a tumor suppressor with sequence homology to protein tyrosine phosphatases and the cytoskeletal protein tensin. mPTEN-mutant mouse embryos display regions of increased proliferation [6].
• The predicted MMAC1 protein contains sequence motifs with significant homology to the catalytic domain of protein phosphatases and to the cytoskeletal proteins, tensin and auxilin [7].
• The phosphatase and tensin homologue deleted on chromosome 10 (PTEN) negatively regulates cell survival and proliferation mediated by phosphoinositol 3 kinases [8].
• Phosphatase and tensin homologue deleted on chromosome ten (PTEN) is part of a complex signaling system that affects a variety of important cell functions [9].
• Tyrosine phosphorylation of Cas, paxillin, and tensin were markedly decreased in VSMCs expressing KI-Src and in src-/- VSMCs [10].

Biological context of Tns1

• Even though tensin is expressed in many different tissues during embryogenesis, tensin null mice developed normally and appeared healthy postnatally for at least several months [1].
• Both thrombin and angII stimulated bundling of actin filaments to form stress fibers, assembly of focal adhesions, and protein tyrosine phosphorylation at focal adhesions, such as p130Cas, paxillin, and tensin [10].
• The importance of the PI3K signalling pathway in regulating the balance of decisions in cell growth, proliferation and survival is clear from the prevalence of oncogenes (e.g. PI3Kalpha) and tumour suppressors [e.g. the PtdIns(3,4,5)P(3) 3-phosphatase, PTEN (phosphatase and tensin homologue deleted on chromosome 10)] found in this pathway [11].
• Overexpression of the tumor suppressor gene phosphatase and tensin homologue partially inhibits wnt-1-induced mammary tumorigenesis [12].
• The tumor suppressor phosphatase and tensin homologue (PTEN) is involved in cell proliferation, adhesion, and apoptosis [12].

Anatomical context of Tns1

• Taken together, our data imply that, in the kidney, loss of tensin leads to a weakening, rather than a severing, of focal adhesion [1].
• Tensin is a focal adhesion molecule that binds to actin filaments and participates in signaling pathways [13].
• Negative regulation of phosphatidylinositol 3-kinase signaling and IL-2-mediated proliferation of CD4(+)CD25(+) T cells is inversely associated with expression of the phosphatase and tensin homologue deleted on chromosome 10, PTEN [14].
• These results suggest that PI 3-kinase interacts with the cytoskeleton via the SH2 domain of tensin and may play an important role in platelet-derived growth factor-induced cytoskeletal reorganization that is concomitant with cell migration and proliferation [15].
• Tensin, which normally segregates into fibrillar adhesions was localized in large focal contacts in the two mutant cell lines, suggesting involvement of pp60(c-src) in the segregation of focal contacts and fibrillar adhesions [16].

Associations of Tns1 with chemical compounds

• Tensin family is a group of focal adhesion proteins that interact with integrins, actin, and phosphotyrosine-containing proteins [17].
• Platelet-derived growth factor-induced formation of tensin and phosphoinositide 3-kinase complexes [15].
• In this study, we have examined the role of the inositol 3-phosphatase and tensin homologue deleted on chromosome 10 (PTEN) in Fc gamma R-induced macrophage function [18].
• Phosphatase and tensin homolog regulation of islet growth and glucose homeostasis [19].
• Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) reduces vascular endothelial growth factor expression in allergen-induced airway inflammation [20].

Physical interactions of Tns1

• Tensin is a focal adhesion phosphoprotein that binds to F-actin and contains a functional Src homology 2 domain [1].

Enzymatic interactions of Tns1

• After confirming the efficiency of glucosylated PEI carriers in lungs, the potential effects of the phosphatase and tensin homologue deleted on chromosome 10 (PTEN) tumor suppressor gene on Akt downstream pathways were investigated [21].
• A most notable finding is that tumorigenesis is accompanied by inactivation of phosphatase and tensin homolog deleted on chromosome 10 (Pten), activation of AKT, fast proliferation and nuclear accumulation of cyclin D1 [22].
• Phagosomes containing IgG-coated particles accumulated 3'-phosphatase and tensin homologue deleted on chromosome 10 and Src homology 2 domain-containing inositol 5'-phosphatase, yet Hp phagosomes did not [23].

Other interactions of Tns1

• Pten (phosphatase with tensin homology), a dual-specificity phosphatase, is a negative regulator of the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway [24].
• Overexpression of a dominant negative Akt mutant or of the tumor suppressor phosphatase and tensin homologue, PTEN, in these cells also caused a significant reduction in MT1-MMP expression and invasion [25].
• The focal adhesion kinase (FAK) functions in regulating tyrosine phosphorylation of several of these proteins, including paxillin, tensin, and p130(cas) [26].
• Moreover, treatment of wild-type cells with tyrphostin AG1007, which inhibits both pp60(c-src) and FAK activity, induced accumulation of tensin in peripheral focal adhesions [16].
• In order to determine the role of pp60(c-src) and related kinases in these processes, we have compared the dynamic reorganization of phosphotyrosine, vinculin, focal adhesion kinase and tensin in cells with altered expression of Src-family kinases [16].

Analytical, diagnostic and therapeutic context of Tns1

• To explore the biological functions of tensin, we cloned the mouse tensin gene, determined its program of expression, and used gene targeting to generate mice lacking tensin [1].

References