Abstract
Human DOCK180, which was originally identified as a major protein bound to the Crk oncogene product, is an archetype of the CDM family of proteins, including Ced-5 of Caenorhabditis elegans and Mbc of Drosophila melanogaster. After DOCK180, at least three putative human proteins that manifest high amino acid sequence similarity to DOCK180 have been registered in the GenBank/EMBL database. We have designated one of them, KIAA0209, as DOCK2 and characterize here. DOCK2 mRNA was expressed mostly in peripheral blood cells, followed by slight expression in the spleen and thymus, whereas DOCK180 was expressed in all tissues tested except in peripheral blood cells. Immunostaining of human cadaver tissues revealed that the expression of DOCK2 was limited to the lymphocytes and macrophages of various organs. DOCK2 bound to and activated Rac1, as did DOCK180; however, DOCK2 did not bind to CrkII, which transduces signals at focal adhesions. Thus, DOCK180 and DOCK2 are regulators of Rac and function in adherent and non-adherent cells, respectively.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Caenorhabditis elegans Proteins*
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Carrier Proteins / chemistry
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Carrier Proteins / isolation & purification
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Carrier Proteins / metabolism*
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DNA, Complementary / chemistry
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GTPase-Activating Proteins
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Guanine Nucleotide Exchange Factors*
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Humans
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Immunohistochemistry
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Leukocytes / metabolism
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Membrane Proteins / chemistry
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Molecular Sequence Data
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Protein Kinases / metabolism
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Proteins / chemistry
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Proteins / metabolism*
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Proto-Oncogene Proteins c-crk
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Proto-Oncogene Proteins*
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RAC2 GTP-Binding Protein
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RNA, Messenger / analysis
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RNA, Messenger / metabolism
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Sequence Homology, Amino Acid
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Spleen / metabolism
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Thymus Gland / metabolism
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rac GTP-Binding Proteins / metabolism
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rac1 GTP-Binding Protein / metabolism
Substances
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BCAP31 protein, human
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CED-5 protein, C elegans
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Caenorhabditis elegans Proteins
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Carrier Proteins
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DNA, Complementary
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DOCK1 protein, human
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DOCK2 protein, human
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GTPase-Activating Proteins
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Guanine Nucleotide Exchange Factors
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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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RNA, Messenger
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Protein Kinases
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rac GTP-Binding Proteins
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rac1 GTP-Binding Protein