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 Mr 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 Mr 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 responsible for faciogenital dysplasia or Aarskog-Scott syndrome. We therefore named p105 frabin (FGD1-related F-actin-binding protein). Frabin bound along the sides of F-actin and showed F-actin-cross-linking activity. Overexpression of frabin in Swiss 3T3 cells and COS7 cells induced cell shape change and c-Jun N-terminal kinase activation, respectively, 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.
Obaishi
H
H
Takai Biotimer Project, ERATO, Japan Science and Technology Corporation, c/o JCR Pharmaceuticals Co., Ltd., 2-2-10 Murotani, Nishi-ku, Kobe 651-2241, Japan.
Nakanishi
H
H
Mandai
K
K
Satoh
K
K
Satoh
A
A
Takahashi
K
K
Miyahara
M
M
Nishioka
H
H
Takaishi
K
K
Takai
Y
Y
D000199:Actins / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001923:Brain Chemistry; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D048429:Cell Size; D002478:Cells, Cultured; D003001:Cloning, Molecular; D004789:Enzyme Activation; D005260:Female; D048031:JNK Mitogen-Activated Protein Kinases; D008840:Microfilament Proteins / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases; D008969:Molecular Sequence Data; D008970:Molecular Weight; D011247:Pregnancy; D011817:Rabbits; D051381:Rats
D000199:Actins; C485164:FGD4 protein, human; C113689:Fgd4 protein, rat; D008840:Microfilament Proteins; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases