Tensin

Tensin was first identified as a 220 kDa multi-domain protein localized to the specialized regions of plasma membrane called integrin-mediated focal adhesions (which are formed around a transmembrane core of an αβ integrin heterodimer).[1] Genome sequencing and comparison have revealed the existence of four tensin genes in humans.[2] These genes appear to be related by ancient instances of gene duplication.

Tensin binds to actin filaments and contains a phosphotyrosine-binding (PTB) domain at the C-terminus, which interacts with the cytoplasmic tail of β integrins. These interactions allow tensin to link actin filaments to integrin receptors. Several factors induce tyrosine phosphorylation of tensin. Thus, tensin functions as a platform for assembly and disassembly of signaling complexes at focal adhesions by recruiting tyrosine-phosphorylated signaling molecules, and also by providing interaction sites for other proteins.[3] Haynie, by contrast, argues in a review of tensin structure and function that experimental evidence for the specific association of tensin with actin filaments is inconclusive at best.[2] It is beyond reasonable doubt, however, that tensin 1, tensin 2 and tensin 3 each contains a protein tyrosine phosphatase (PTP) domain near the N-terminus. The PTP domain is unlikely to be active in tensin 1, owing to mutation of the essential nucleophilic cysteine in the signature motif to asparagine.[4] Nevertheless, phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase, the well-studied tumor suppressor that is better known as PTEN, gets its name from homology with PTPs and tensin 1.[5] More detailed structure comparisons have revealed that tensins 1-3, PTEN, auxilin[4] and other proteins in animals, plants and fungi comprise a PTP-C2 superdomain.[6] An integrated PTP domain and C2 domain, the PTP-C2 superdomain came into existence over 1 billion years ago and has functioned as a single heritable unit since then.

The first tensin cDNA sequence was isolated from chicken.[7] Analysis of knockout mice has demonstrated critical roles of tensin in renal function, muscle regeneration, and cell migration. Evidence is now emerging to suggest tensin is an important component linking the ECM, the actin cytoskeleton, and signal transduction. Therefore, tensin and its downstream signaling molecules may be targets for therapeutic interventions in renal disease, wound healing and cancer.

References

  1. ↑ Le Clainche, C; Carlier, MF (2008). "Regulation of actin assembly associated with protrusion and adhesion in cell migration.". Physiological reviews 88 (2): 489–513. doi:10.1152/physrev.00021.2007. PMID 18391171.
  2. 1 2 Haynie, Donald T. (2014). "Molecular physiology of the tensin brotherhood of integrin adaptor proteins". Proteins: Structure, Function, and Bioinformatics 82: 1113–1127. doi:10.1002/prot.24560. PMID 24634006.
  3. ↑ Lo, Su Hao (2004). "Tensin". The International Journal of Biochemistry & Cell Biology 36 (1): 31–34. doi:10.1016/S1357-2725(03)00171-7. PMID 14592531.
  4. 1 2 Haynie, Donald T.; Ponting, Christopher P. (1996). "The N-terminal domains of tensin and auxilin are phosphatase homologues". Protein Science 5: 2643–2646. doi:10.1002/pro.5560051227. PMC 2143309. PMID 8976573.
  5. ↑ Li J, Yen C, Liaw D, Podsypanina K, Bose S, Wang SI, Puc J, Miliaresis C, Rodgers L, McCombie R, Bigner SH, Giovanella BC, Ittmann M, Tycko B, Hibshoosh H, Wigler MH, Parsons R (March 1997). "PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer". Science 275 (5308): 1943–7. doi:10.1126/science.275.5308.1943. PMID 9072974.
  6. ↑ Haynie, Donald T.; Xue, Bin (2015). "Superdomains in the protein structure hierarchy: the case of PTP-C2". Protein Science 24: 874–882. doi:10.1002/pro.2664. PMID 25694109.
  7. ↑ Davis, S; Lu, ML; Lo, SH; Lin, S; Butler, JA; Druker, BJ; Roberts, TM; An, Q; Chen, LB (1991). "Presence of an SH2 domain in the actin-binding protein tensin.". Science 252 (5006): 712–5. doi:10.1126/science.1708917. PMID 1708917.

External links

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