Tensin is an actin-binding protein that is localized in focal adhesions. At focal adhesion sites, tensin participates in the protein complex that establishes transmembrane linkage between the extracellular matrix and cytoskeletal actin

Tensin is a focal adhesion molecule that binds to actin filaments through its N terminus (Lo et al., 1994a; Lo et al., 1994b; Chuang et al., 1995). In addition, it contains two functional motifs, including a Src homology domain 2 (SH2) and a phosphotyrosine binding (PTB) domain (Davis et al., 1991; Chen et al., 2000; Chen et al., 2002). This conserved domain structure gives significant clues to its possible function, including potential roles in cell signaling. Tensin is best known as an adaptor protein linking integrin to the actin cytoskeleton. Integrins are a family of the transmembrane receptors that are localized in focal adhesions (Hynes, 1992). The extracellular domain of integrin interacts with the extracellular matrix, and its cytoplasmic domain anchors actin filaments to the plasma membrane through the focal adhesion protein complex (Burridge et al., 1988; Hynes, 1992; Lo et al., 1994a; Jockusch et al., 1995). Integrin is also believed to participate in diverse biological events such as cytoskeletal restructuring, cell motility and even cell survival via focal adhesion complexes that include tensin, focal adhesion kinase (FAK), Src kinase and protein kinase C (Burridge et al., 1988; Schwartz et al., 1995; Giancotti and Ruoslahti, 1999). Most interestingly, integrin is involved in various cell signaling pathways through its association with focal adhesion proteins. For example, integrin activates ERKMAP kinase by promoting the SH2 domain-mediated association of Grb2 with tyrosine kinases such as FAK and c-Src in focal adhesions (Schlaepfer et al., 1994). The phosphoinositide 3 kinase (PI3K)-dependent signaling pathway is also activated by integrin through FAK-dependent mechanism (Chen and Guan, 1994; Shaw et al., 1997; Reiske et al., 1999). In addition, several reports have demonstrated that JNK is also activated by integrins when cells are attached to the extracellular matrix (Miranti et al., 1998; Oktay et al., 1999). The role of tensin as an adaptor for integrin and as a required component in focal adhesions suggests the possibility that it may act as a mediator of integrin signaling. In support of this idea, much indirect and direct evidence has been collected. Previously, the SH2 and PTB domains in the C terminus of tensin have been demonstrated to bind tyrosine phosphorylated proteins such as PI3K and p130 CAS (Salgia et al., 1995; Salgia et al., 1996; Auger et al., 1996). In addition, tensin itself is phosphorylated at serine, threonine and tyrosine residues when cells are stimulated by either cell adhesion (Bockholt and 4001 Development 130, 4001-4010 © 2003 The Company of Biologists Ltd doi:10.1242/dev.00595