Isolation of a novel human gene, ARHGAP9, encoding a rho-GTPase activating protein.
Members of the Rho family of small guanosine triphosphatases (Rho-GTPases) have emerged as key coordinators of signaling pathways leading to remodeling of the actin cytoskeleton, a process that plays a critical role in cell adhesion and migration. However, the precise regulatory mechanisms remain to be elucidated. Here we report isolation of a novel human gene, ARHGAP9, which encodes a protein containing a Rho-GTPase activating protein (Rho-GAP) domain, a src-homology 3 (SH3) domain, a pleckstrin homology (PH) region, and a WW domain. In vitro, the recombinant protein revealed substantial GAP activity toward Cdc42Hs and Rac1, and less toward RhoA. The transcript was predominantly expressed in peripheral blood leukocytes, spleen, and thymus. Exogenous expression of the entire coding region of ARHGAP9 into human leukemia KG-1 cells repressed adhesion of the cells to fibronectin and collagen IV. Our results indicate that ARHGAP9 is involved in regulating adhesion of hematopoietic cells to extracellular matrix.
Furukawa
Y
Y
Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
Kawasoe
T
T
Daigo
Y
Y
Nishiwaki
T
T
Ishiguro
H
H
Takahashi
M
M
Kitayama
J
J
Nakamura
Y
Y
D000595:Amino Acid Sequence; D002448:Cell Adhesion; D003001:Cloning, Molecular; D005353:Fibronectins / Q000378:metabolism; D020690:GTPase-Activating Proteins / Q000235:genetics* / Q000502:physiology*; D005796:Genes; D006160:Guanosine Triphosphate / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000096:biosynthesis; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism*
C431580:ARHGAP9 protein, human; D005353:Fibronectins; D020690:GTPase-Activating Proteins; D012333:RNA, Messenger; D006160:Guanosine Triphosphate; D020764:cdc42 GTP-Binding Protein; D020830:rac1 GTP-Binding Protein; D020741:rho GTP-Binding Proteins