Abstract
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.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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3T3 Cells
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ADP-Ribosylation Factors / metabolism*
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Amino Acid Sequence
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Animals
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COS Cells
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Carrier Proteins / genetics*
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Carrier Proteins / metabolism*
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Cell Adhesion
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Cell Movement
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Cloning, Molecular
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GTPase-Activating Proteins / genetics*
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GTPase-Activating Proteins / metabolism*
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Golgi Apparatus / metabolism
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HeLa Cells
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Humans
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Mice
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Molecular Sequence Data
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Phosphatidylinositols / metabolism*
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Proteins / genetics*
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Proteins / metabolism*
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Sequence Alignment
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Signal Transduction*
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rho GTP-Binding Proteins / metabolism*
Substances
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ARAP1 protein, human
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ARAP2 protein, human
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Carrier Proteins
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GTPase-Activating Proteins
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Phosphatidylinositols
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Proteins
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phosphoinositide-3,4,5-triphosphate
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ADP-Ribosylation Factors
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rho GTP-Binding Proteins
Associated data
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GENBANK/AY049732
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GENBANK/AY049733