Phosphatidylinositol 3-kinase and Src family kinases are required for phosphorylation and membrane recruitment of Dok-1 in c-Kit signaling Journal Article

  


Authors: Liang, X.; Wisniewski, D.; Strife, A.; Shivakrupa; Clarkson, B.; Resh, M. D.
Article Title: Phosphatidylinositol 3-kinase and Src family kinases are required for phosphorylation and membrane recruitment of Dok-1 in c-Kit signaling
Abstract: Dok-1 is an adaptor protein that is a substrate for Bcr-Ab1 and other tyrosine protein kinases. The presence of pleckstrin homology and phosphotyrosine binding domains as well as multiple tyrosine phosphorylation sites suggests that Dok-1 is involved in protein-protein and/or protein-lipid interactions. Here we show that stimulation of Mo7 hematopoietic cells with c-Kit ligand (KL) induces phosphatidylinositol (PI) 3-kinase-dependent tyrosine phosphorylation and membrane recruitment of Dok-1. Addition of the K-Ras membrane-targeting motif to Dok-1 generated a constitutively membrane-bound Dok-1 protein whose tyrosine phosphorylation was independent of PI 3-kinase. Membrane localization of Dok-1 was required for its ability to function as a negative regulator of cell proliferation. Additional experiments revealed that Dok-1 associated with the juxtamembrane region and C-terminal tail of c-Kit. Lyn promoted phosphorylation of c-Kit and association of c-Kit and Dok-1. Both Lyn and Tec were capable of phosphorylating Dok-1. However, the use of primary bone marrow mast cells from normal and Lyn-deficient mice demonstrated that Lyn is required for KL-dependent Dok-1 tyrosine phosphorylation. Taken together, these data indicate that activation of PI 3-kinase by KL promotes binding of the Dok pleckstrin homology domain and Dok-1 recruitment to the plasma membrane where Dok-1 is phosphorylated by Src and/or Tec family kinases.
Keywords: signal transduction; controlled study; protein phosphorylation; unclassified drug; human cell; dna-binding proteins; protein localization; cell proliferation; animals; mice; cell division; stem cell factor; proto-oncogene proteins c-kit; carboxy terminal sequence; protein protein interaction; cell line; protein binding; transfection; protein tyrosine kinase; tyrosine; cos cells; phosphorylation; phosphatidylinositol 3 kinase; rna-binding proteins; recombinant fusion proteins; enzyme inhibitors; cell membrane; 1-phosphatidylinositol 3-kinase; glutathione transferase; cell strain cos1; hematopoietic cell; phosphoproteins; binding site; protein structure, tertiary; bcr abl protein; sequence homology; src-family kinases; biochemistry; proto-oncogene proteins p21(ras); lipid metabolism; electrophysiology; subcellular fractions; enzymes; wortmannin; dna, complementary; phosphotyrosine; protein lipid interaction; cells; protein dok 1; adaptor protein; mast cell; chemical bonds; biological membranes; androstadienes; precipitin tests; dna transfection; pleckstrin; humans; human; priority journal; article; membrane localization
Journal Title: Journal of Biological Chemistry
Volume: 277
Issue: 16
ISSN: 0021-9258
Publisher: American Society for Biochemistry and Molecular Biology  
Date Published: 2002-04-19
Start Page: 13732
End Page: 13738
Language: English
DOI: 10.1074/jbc.M200277200
PUBMED: 11825908
PROVIDER: scopus
DOI/URL:

http://www.scopus.com/inward/record.url?eid=2-s2.0-0037134428&partnerID=40&md5=a1dd2938eb86883cd0fd226b8de73204
Notes: Export Date: 14 November 2014 -- Source: Scopus
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MSK Authors
  1. Xiquan Liang
    9 Liang
  2. Marilyn D Resh
    120 Resh
  3. David Wisniewski
    37 Wisniewski
  4. Bayard Clarkson
    220 Clarkson
  5. Annabel Strife
    41 Strife
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