PIST: a novel PDZ/coiled-coil domain binding partner for the rho-family GTPase TC10.
TC10 is a member of the Rho family of GTPases, most closely related to Cdc42. This family of proteins mediates cytoskeletal rearrangements, activation of signal transduction cascades, and activation of gene transcription. A current focus is to identify and characterize the GTPase effectors that are involved in these cellular events. Many specific effectors for Cdc42 have been identified, most of which bind equally well to TC10, though a subset has only a low affinity for TC10. No protein that specifically interacts with TC10 has yet been described. Here, we report the cloning and characterization of PIST, a TC10-specific interacting protein. PIST possesses a PDZ domain and two, putative, coiled-coil domains, one of which contains a leucine zipper. It interacts directly and specifically with TC10:GTP, though with low affinity, and a mutation within the effector binding domain of TC10 disrupts the interaction. PIST also forms homodimers. The first coiled-coil and PDZ domains are not necessary for these interactions, but deletion of the N-terminal portion of the leucine zipper abolishes dimerization. PIST may function as a scaffolding protein to link TC10 to signaling pathways.