|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
50
|
|
pubmed:dateCreated |
2000-1-13
|
|
pubmed:abstractText |
SHP-1 plays key roles in the modulation of hematopoietic cell signaling. To ascertain the impact of SHP-1 on colony-stimulating factor-1 (CSF-1)-mediated survival and proliferative signaling, we compared the CSF-1 responses of primary bone marrow macrophages (BMM) from wild-type and SHP-1-deficient motheaten (me/me) mice. CSF-1-induced protein tyrosine phosphorylation levels were similar in wild-type and me/me BMM, except for the constitutive hyperphosphorylation of a 62-kDa phosphoprotein (pp62) in me/me macrophages. pp62 was identified as the RASGAP-associated p62(DOK) and was shown to be the major CSF-1R-associated tyrosine-phosphorylated protein in CSF-1-treated BMM. p62(DOK) was found to be constitutively associated with SHP-1 in BMM and in 293T cells, co-expressing p62(dok) and either wild-type or catalytically inert SHP-1 (SHP-1 C453S). In both cell types, the interaction of SHP-1 with p62(DOK) occurred independently of p62(DOK) tyrosine phosphorylation, but only the tyrosine-phosphorylated p62(DOK) was bound by SHP-1 C453S in a far Western analysis. These findings suggest a constitutive association of SHP-1 and p62(DOK) that is either conformation-dependent or indirect as well as a direct, inducible association of the SHP-1 catalytic domain with tyrosine-phosphorylated p62(DOK). p62(DOK) hyperphosphorylation is not associated with altered CSF-1-induced RAS signaling or proliferation. However, whereas wild-type macrophages undergo cell death following CSF-1 removal, me/me macrophages exhibit prolonged survival in the absence of growth factor. Thus, p62(DOK) is a major SHP-1 substrate whose tyrosine phosphorylation correlates with growth factor-independent survival in macrophages.
|
|
pubmed:grant |
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/DOK1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Dok1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/GAP-associated protein p62,
http://linkedlifedata.com/resource/pubmed/chemical/Glutathione Transferase,
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Macrophage Colony-Stimulating Factor,
http://linkedlifedata.com/resource/pubmed/chemical/PTPN11 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/PTPN6 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphotyrosine,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Tyrosine Phosphatase...,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Tyrosine Phosphatase...,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Tyrosine Phosphatases,
http://linkedlifedata.com/resource/pubmed/chemical/Ptpn11 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Ptpn6 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/RNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/SH2 Domain-Containing Protein...
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Dec
|
|
pubmed:issn |
0021-9258
|
|
pubmed:author |
|
|
pubmed:issnType |
Print
|
|
pubmed:day |
10
|
|
pubmed:volume |
274
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
35855-65
|
|
pubmed:dateRevised |
2007-11-15
|
|
pubmed:meshHeading |
pubmed-meshheading:10585470-Animals,
pubmed-meshheading:10585470-Bone Marrow Cells,
pubmed-meshheading:10585470-Cell Line,
pubmed-meshheading:10585470-Cells, Cultured,
pubmed-meshheading:10585470-DNA-Binding Proteins,
pubmed-meshheading:10585470-Glutathione Transferase,
pubmed-meshheading:10585470-Humans,
pubmed-meshheading:10585470-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:10585470-Macrophage Colony-Stimulating Factor,
pubmed-meshheading:10585470-Macrophages,
pubmed-meshheading:10585470-Mice,
pubmed-meshheading:10585470-Mice, Mutant Strains,
pubmed-meshheading:10585470-Phosphoproteins,
pubmed-meshheading:10585470-Phosphorylation,
pubmed-meshheading:10585470-Phosphotyrosine,
pubmed-meshheading:10585470-Protein Tyrosine Phosphatase, Non-Receptor Type 11,
pubmed-meshheading:10585470-Protein Tyrosine Phosphatase, Non-Receptor Type 6,
pubmed-meshheading:10585470-Protein Tyrosine Phosphatases,
pubmed-meshheading:10585470-RNA-Binding Proteins,
pubmed-meshheading:10585470-Recombinant Fusion Proteins,
pubmed-meshheading:10585470-SH2 Domain-Containing Protein Tyrosine Phosphatases,
pubmed-meshheading:10585470-Transfection,
pubmed-meshheading:10585470-src Homology Domains
|
|
pubmed:year |
1999
|
|
pubmed:articleTitle |
SHP-1 regulation of p62(DOK) tyrosine phosphorylation in macrophages.
|
|
pubmed:affiliation |
Department of Developmental Biology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
|
|
pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
|
