HETEROPHILIC INTERACTION BETWEEN BCH DOMAINS OF BNIP-2 AND BPGAPI REGULATES RHOA SIGNALING

Abstract

BPGAP1 (BNIP-2 and Cdc42GAP Homology [BCH] domain-containing, Proline-rich and Cdc42GAP-like protein 1) is a multi-domain GTPase-activating protein (GAP) that exerts catalytic activity specifically towards RhoA. Through engagement of interacting partners including cortactin and EEN/endophilin II, BPGAP1 facilitates cell migration and EGF receptor endocytosis for ERK1/2 activation, respectively. On the other hand, association with other interacting partners could serve regulatory purposes. For instance, release of auto-inhibition within BPGAP1 by active MEK2 allows Pin1 to suppress BPGAP1-induced acute ERK activation and attenuate Rho signaling. On-going research on other interacting partners also reveal that these proteins could negatively regulate the effect of BPGAP1 on Ras activation. Based on earlier work, BNIP-2 (Bcl-2 and E1B Nineteen kDa Interacting Protein-2) interacts with BPGAP1, potentially through their BCH domains. In this current study, through use of immunoprecipitation and immunofluorescence studies, RhoA activity and physiological assays, we examined the significance, as well as possible mechanism underlying BNIP-2-BPGAP1 interaction.