Ras And Rab Interactor 1 (RIN1)

RIN1 protein resides primarily at the plasma membrane, where RAS is localized. RIN1 was not able to interact with either an effector mutant or a dominant-negative mutant of RAS. The interaction between RAS and RIN1 is enhanced when RAS was bound to GTP and is dependent on RAS activation.Optimal binding requires some or all of the 62 amino acids that are missing in the shorter RIN1 splice variant. Overexpression of the identified RAS-binding domain of RIN1 in mammalian cells leads to a block in RAS-mediated signaling. Using 2-hybrid experiments, the authors demonstrated that the RAS-binding domain of RIN1, like that of RAF1, can bind to murine 14-3-3 protein family members including the epsilon (YWHAE), beta (YWHAB), and zeta (YWHAZ) isoforms.