FRABIN, A NOVEL FGD1-RELATED ACTIN FILAMENT-BINDING PROTEIN CAPABLE OF CHANGING CELL-SHAPE AND ACTIVATING C-JUN N-TERMINAL KINASE

We purified from rat brain a novel F-actin-binding protein with a M-r of about 105,000 (p105), which was estimated by SDS-polyacrylamide gel electrophoresis. We cloned its cDNA from a rat brain cDNA library and characterized it, p105 was a protein of 766 amino acids and showed a calculated M-r of 86,449. p105 consisted of one F-actin-binding domain at the N-terminal region, one Dbl homology domain and one pleckstrin homology domain at the middle region, and one cysteine-rich domain at the C-terminal region. This domain organization of p105 was similar to that of FGD1, which has been determined to be the genetic locus respo nsible for facio-genital dysplasia or Aarskog-Scott syndrome. We there fore named p105 frabin (FGD1-related F-actin-binding protein). Frabin bound along the sides of F-actin and showed F-actin-cross-linking acti vity. Overexpression of frabin in Swiss 3T3 cells and COS7 cells induc ed cell shape change and c-Jun N-terminal kinase activation, respectiv ely, as described for FGD1. Because FGD1 has been shown to serve as a GDP/GTP exchange protein for Cdc42 small G protein, it is likely that frabin is a direct linker between Cdc42 and the actin cytoskeleton.