ARAP1: a point of convergence for Arf and Rho signaling.
We have identified ARAP1 and ARAP2 and examined ARAP1 as a possible link between phosphoinositide-, Arf-, and Rho-mediated cell signaling. ARAP1 contains Arf GAP, Rho GAP, Ankyrin repeat, Ras-associating, and five PH domains. In vitro, ARAP1 had Rho GAP and phosphatidylinositol (3,4,5) trisphosphate (PIP3)-dependent Arf GAP activity. ARAP1 associated with the Golgi. The Rho GAP activity mediated cell rounding and loss of stress fibers when ARAP1 was overexpressed. The Arf GAP activity mediated changes in the Golgi apparatus and the formation of filopodia, the latter a consequence of increased cellular activity of Cdc42. The Arf GAP and Rho GAP activities both contributed to inhibiting cell spreading. Thus, ARAP1 is a PIP3-dependent Arf GAP that regulates Arf-, Rho-, and Cdc42-dependent cell activities.
Miura
Koichi
K
Laboratory of Cellular Oncology, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
Jacques
Kerry M
KM
Stauffer
Stacey
S
Kubosaki
Atsutaka
A
Zhu
Kejin
K
Hirsch
Dianne Snow
DS
Resau
James
J
Zheng
Yi
Y
Randazzo
Paul A
PA
D016475:3T3 Cells; D020727:ADP-Ribosylation Factors / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D002448:Cell Adhesion; D002465:Cell Movement; D003001:Cloning, Molecular; D020690:GTPase-Activating Proteins / Q000235:genetics* / Q000378:metabolism*; D006056:Golgi Apparatus / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D010716:Phosphatidylinositols / Q000378:metabolism*; D011506:Proteins / Q000235:genetics* / Q000378:metabolism*; D016415:Sequence Alignment; D015398:Signal Transduction; D020741:rho GTP-Binding Proteins / Q000378:metabolism*
C446513:ARAP1 protein, human; C446514:ARAP2 protein, human; D002352:Carrier Proteins; D020690:GTPase-Activating Proteins; D010716:Phosphatidylinositols; D011506:Proteins; C118303:phosphoinositide-3,4,5-triphosphate; D020727:ADP-Ribosylation Factors; D020741:rho GTP-Binding Proteins