Abstract
DOCK180 is involved in integrin signaling through CrkII-p130(Cas) complexes. We have studied the involvement of DOCK180 in Rac1 signaling cascades. DOCK180 activated JNK in a manner dependent on Rac1, Cdc42Hs, and SEK, and overexpression of DOCK180 increased the amount of GTP-bound Rac1 in 293T cells. Coexpression of CrkII and p130(Cas) enhanced this DOCK180-dependent activation of Rac1. Furthermore, we observed direct binding of DOCK180 to Rac1, but not to RhoA or Cdc42Hs. Dominant-negative Rac1 suppressed DOCK180-induced membrane spreading. These results strongly suggest that DOCK180 is a novel activator of Rac1 and involved in integrin signaling.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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3T3 Cells
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Animals
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Calcium-Calmodulin-Dependent Protein Kinases / physiology
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Enzyme Activation
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GTP Phosphohydrolases / physiology
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GTP-Binding Proteins / physiology*
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Integrins / metabolism
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JNK Mitogen-Activated Protein Kinases
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Membrane Proteins / biosynthesis
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Mice
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Mitogen-Activated Protein Kinases*
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Protein Binding
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Protein Biosynthesis
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Proteins / metabolism
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Proteins / physiology*
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Proto-Oncogene Proteins / metabolism*
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Proto-Oncogene Proteins c-crk
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Signal Transduction / physiology
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rac GTP-Binding Proteins
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src Homology Domains*
Substances
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DOCK1 protein, human
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Integrins
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Membrane Proteins
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Proteins
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-crk
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Calcium-Calmodulin-Dependent Protein Kinases
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JNK Mitogen-Activated Protein Kinases
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Mitogen-Activated Protein Kinases
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GTP Phosphohydrolases
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GTP-Binding Proteins
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rac GTP-Binding Proteins