GDAP2 AS A NOVEL REGULATORY SCAFFOLD FOR RAS-ERK SIGNALING IN CELL GROWTH AND DIFFERENTIATION

Abstract

RAS GTPASES REGULATE DIVERSE CELLULAR EVENTS INCLUDING PROLIFERATION, MIGRATION, APOPTOSIS AND DIFFERENTIATION. THEY CYCLE BETWEEN ACTIVE GTP-BOUND FORM AND INACTIVE GDP-BOUND FORM AND ARE TIGHTLY REGULATED BY GUANINE NUCLEOTIDE EXCHANGE FACTORS (GEFS) AND GTPASE-ACTIVATING PROTEINS (GAPS). HOWEVER, LITTLE IS KNOWN ABOUT HOW THE REGULATORY NETWORK OF GTPASES, GEFS AND GAPS ARE COORDINATED. WORK FROM OUR GROUP HAS SHOWN THAT BNIP-2 AND CDC42GAP HOMOLOGY (BCH) DOMAIN-CONTAINING PROTEINS SERVE AS REGULATORY SCAFFOLDS FOR SMALL GTPASES SIGNALING BY TARGETING SMALL GTPASES AS WELL AS THEIR IMMEDIATE GEFS AND GAPS. GDAP2 (GANGLIOSIDES-INDUCED DIFFERENTIATION ASSOCIATED PROTEIN 2) IS A NOVEL BCH DOMAIN-CONTAINING PROTEIN THAT IS FOUND UP-REGULATED DURING NEURONAL DIFFERENTIATION OF NEURO2A AND P19 CELLS BUT IS ALSO UBIQUITOUSLY EXPRESSED. HOWEVER, ITS ROLE(S) AND MECHANISM OF ACTION IN CELL DYNAMICS REMAINS UNKNOWN. HERE, I SHOWED THAT ECTOPIC EXPRESSION OF GDAP2 PROMOTED RAS ACTIVATION AND I