Function of BPGAPI in RAS-Mediated neuronal differentiation

Abstract

BPGAP1 (BNIP-2 Cdc42GAP Homology (BCH) domain containing, Proline rich and Cdc42 GAP like protein subtype-1) is a multifunctional RhoGAP, involved in pseudopodia formation and cell migration. The RhoGAP domain of BPGAP1 interacts with Pin1, while, active Mek2 enhances Pin1 binding to BPGAP1, suppressing BPGAP1- induced acute Erk activation and cell migration. Proteomics pull down revealed novel interacting partners for BPGAP1 namely: Cortactin, which interacts with the proline rich region of BPGAP1 and causes cell migration; while EEN interacts with BPGAP1 enhancing EEN mediated receptor endocytosis, resulting in Ras/MAPK pathway activation. Current work has demonstrated a role for BPGAP1 in Ras signaling, through its interaction with another uncharacterized binding partner. This interaction modulates Ras signaling in an isoform specific manner and regulates differentiation of PC12 cells via a GAP independent manner. The mechanism, function and significance of these interactions will be addressed.