Roles of BPGAP1 in cell signalling - Filling in the "GAP" in cell dynamics control

Abstract

<P>RHO GTPASES ARE IMPORTANT REGULATORS FOR CELL DYNAMICS. THEY ARE ACTIVATED BY GUANINE NUCLEOTIDE EXCHANGE FACTORS AND INACTIVATED BY GTPASE-ACTIVATING PROTEINS (GAPS). WE RECENTLY IDENTIFIED BPGAP1 AS A NOVEL RHOGAP THAT REGULATES PSEUDOPODIA AND CELL MIGRATION VIA THE INTERPLAY OF ITS BNIP-2 AND CDC42GAP HOMOLOGY DOMAIN, RHOGAP DOMAIN AND PROLINE-RICH REGION. TO FURTHER ELUCIDATE ITS ROLES IN CELL DYNAMICS CONTROL, WE EMPLOYED PROTEIN PRECIPITATIONS AND MATRIX-ASSISTED LASER DESORPTION/IONIZATION MASS-SPECTROMETRY AND IDENTIFIED CORTACTIN AND EEN/ENDOPHILIN II AS NOVEL PARTNERS OF BPGAP1. PROGRESSIVE DELETION AND SITE-DIRECTED MUTAGENESIS STUDIES CONFIRMED THAT THEY INTERACTED DIRECTLY WITH THE PROLINES AT 184 AND 186 OF BPGAP1 VIA THEIR SRC HOMOLOGY-3 DOMAIN. WE FURTHER SHOWED THAT BPGAP1 INTERACTION WITH CORTACTIN FACILITATED CORTACTIN TRANSLOCATION TO THE PERIPHERY FOR ENHANCED CELL MIGRATION AND THAT THE OVEREXPRESSION OF EEN AND BPGAP1 ENHANCED EGF-STIMULATED RECEPTOR ENDOCYTO