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 Cdc4 2, This family of proteins mediates cytoskeletal rearrangements, activation of signal transduction cascades, and activation of gene transcription. A c urrent focus is to identify and characterize the GTPase effecters that are involved in these cellular events. Many specific effecters for Cdc42 have b een identified, most of which bind equally well to TC10, though a subset ha s only a low affinity for TC10. No protein that specifically interacts with TC10 has yet been described. Here, we report the cloning and characterizat ion of FIST, a TC10-specific interacting protein. FIST possesses a PDZ doma in and two, putative, coiled-coil domains, one of which contains a leucine zipper. It interacts directly and specifically with TC10:GTP, though with l ow affinity, and a mutation within the effector binding domain of TC10 disr upts the interaction. FIST 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. FIST may f unction as a scaffolding protein to link TC10 to signaling pathways, (C) 20 01 Academic Press.