Shin Lin and Diane C. Lin
Dept. of Biophysics, Johns Hopkins University, Baltimore, MD 21218
Tensin (Mr = 215,000) was first identified as a barbed-end actin capping protein immunolocalized at various adherent junctions (e.g., focal adhesions of fibroblasts) and Z-lines of muscle (Wilkins et al., J. Cell Biol., 103, 1483-1494, 1986). Subsequent research involving molecular cloning, sequence analysis, and binding assays on fusion proteins containing truncated tensin revealed a number of domains/sites of biological interest. Several of these domains are related to actin: (a) S1061-H1145, containing high-affinity capping activity (Chuang et al., J. Cell Biol., 128, 1095-1109, 1995); (b) L419-N443 with homology to the actin binding site in dimeric cross-linking proteins such as spectrin; (c) D1739-E1767 with homology to the actin binding site of myosin; (d) M49-T78 with homology to actin residues 221-249 involved in subunit contact in F-actin; and (e) L673-H707 with homology to actin residues 291-321. Tensin also has specific binding sites for vinculin (within N790-K1060) and for the cytoplasmic tail of beta-1 integrin (within S1061-Y1521). In addition, tensin has an SH2 domain (W1520-P1628) for binding phosphotyrosyl residues (Davis et al., Science, 252, 712-715), and fibroblast tensin itself has phosphorylated tyrosine, serine, threonine, with the former increasing with oncogenic transformation and growth factor stimulation. Other investigators had shown that when signal transduction is initiated by aggregation of integrin with antibodies, tensin is the first cytoskeletal protein (together with focal adhesion kinase) to appear in the clusters. The studies on tensin domains/sites to date strongly suggest that it plays a direct role in linking F-actin to the cell membrane as well as in integrin-mediated signal transduction. (Supported by NIH GM22289).