Abstract
Integrin binding to extracellular matrix proteins induces formation of signaling complexes at focal adhesions. Zyxin co-localizes with integrins at sites of cell-substratum adhesion and is postulated to serve as a docking site for the assembly of multimeric protein complexes involved in regulating cell motility. Recently, we identified a new member of the zyxin family called TRIP6. TRIP6 is localized at focal adhesions and overexpression of TRIP6 slows cell migration. In an effort to define the molecular mechanism by which TRIP6 affects cell migration, the yeast two-hybrid assay was employed to identify proteins that directly bind to TRIP6. This assay revealed that both TRIP6 and zyxin interact with CasL/HEF1, a member of the Cas family. This association is mediated by the LIM region of the zyxin family members and the SH2 domain-binding region of CasL/HEF1. Furthermore, the association between p130(Cas) and the two zyxin family members was demonstrated to occur in vivo by co-immunoprecipitation. Zyxin and Cas family members may cooperate to regulate cell motility.
Highlights
Integrin-mediated cell adhesion to extracellular matrix (ECM)1 components is crucial for many cell activities including cell survival, proliferation, migration, and differentiation [1,2,3,4,5]
We report that like zyxin, endogenous TRIP6 is localized at focal adhesions
We demonstrate that overexpression of TRIP6 results in decreased cell migration
Summary
Integrin-mediated cell adhesion to extracellular matrix (ECM) components is crucial for many cell activities including cell survival, proliferation, migration, and differentiation [1,2,3,4,5]. The NH2-terminal proline-rich region of zyxin displays four proline-rich repeats that serve as docking sites for Mena (mammalian Ena) and VASP (vasodilator-activated phosphoprotein) [36, 41, 42], proteins that are postulated to play an important role in the assembly and dynamics of actin filaments [42,43,44]. As is the case for the proline-rich sequences in the NH2 terminus of zyxin, the COOH-terminal LIM domains of zyxin are predicted to mediate a series of protein-protein interactions [40, 50]. The most NH2-terminal LIM domain (LIM1) of zyxin interacts with members of the cysteine-rich protein family that play important roles in muscle [40, 51].
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