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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
8
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pubmed:dateCreated |
2006-4-20
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pubmed:abstractText |
The development of macrophages from myeloid progenitor cells is primarily controlled by the growth factor colony stimulating factor-1 (CSF-1) and its cognate receptor, a transmembrane tyrosine kinase encoded by the c-Fms proto-oncogene. The CSF-1 receptor exerts its biological effects on cells via a range of signaling proteins including Erk1/2 and Akt. Here we have investigated the potential involvement of the Src-like adapter protein (SLAP-2) in signaling by the CSF-1 receptor in mouse bone marrow-derived macrophages. RT-PCR analysis revealed constitutive expression of the SLAP-2 gene in bone marrow macrophages. Surprisingly, co-immunoprecipitation and GST binding experiments demonstrated that the CSF-1 receptor could bind to SLAP-2 in a ligand-independent manner. Furthermore, the binding of SLAP-2 to the CSF-1 receptor involved multiple domains of SLAP-2. SLAP-2 also bound c-Cbl, with the interaction being mediated, at least in part, by the unique C-terminal domain of SLAP-2. Overexpression of SLAP-2 in bone marrow macrophages partially suppressed the CSF-1-induced tyrosine phosphorylation and/or expression level of a approximately 80 kDa protein without affecting CSF-1-induced global tyrosine phosphorylation, or activation of Akt or Erk1/2. Significantly, CSF-1 stimulation induced serine phosphorylation of SLAP-2. Pharmacologic inhibition of specific protein kinases revealed that CSF-1-induced phosphorylation of SLAP-2 was dependent on JNK activity. Taken together, our results suggest that SLAP-2 could potentially be involved in signaling by the CSF-1 receptor.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Ligands,
http://linkedlifedata.com/resource/pubmed/chemical/MAP Kinase Kinase 4,
http://linkedlifedata.com/resource/pubmed/chemical/Macrophage Colony-Stimulating Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-cbl,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins pp60(c-src),
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Macrophage...,
http://linkedlifedata.com/resource/pubmed/chemical/Serine,
http://linkedlifedata.com/resource/pubmed/chemical/Sla protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Tyrosine
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
1742-464X
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
273
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1791-804
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:16623714-Amino Acid Sequence,
pubmed-meshheading:16623714-Animals,
pubmed-meshheading:16623714-Bone Marrow,
pubmed-meshheading:16623714-Female,
pubmed-meshheading:16623714-Humans,
pubmed-meshheading:16623714-Kidney,
pubmed-meshheading:16623714-Ligands,
pubmed-meshheading:16623714-MAP Kinase Kinase 4,
pubmed-meshheading:16623714-Macrophage Colony-Stimulating Factor,
pubmed-meshheading:16623714-Macrophages,
pubmed-meshheading:16623714-Mice,
pubmed-meshheading:16623714-Mice, Inbred C57BL,
pubmed-meshheading:16623714-Mitogen-Activated Protein Kinase 1,
pubmed-meshheading:16623714-Mitogen-Activated Protein Kinase 3,
pubmed-meshheading:16623714-Molecular Sequence Data,
pubmed-meshheading:16623714-Phosphorylation,
pubmed-meshheading:16623714-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:16623714-Proto-Oncogene Proteins c-cbl,
pubmed-meshheading:16623714-Proto-Oncogene Proteins pp60(c-src),
pubmed-meshheading:16623714-Receptor, Macrophage Colony-Stimulating Factor,
pubmed-meshheading:16623714-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:16623714-Sequence Homology, Amino Acid,
pubmed-meshheading:16623714-Serine,
pubmed-meshheading:16623714-Signal Transduction,
pubmed-meshheading:16623714-Tyrosine
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pubmed:year |
2006
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pubmed:articleTitle |
A potential role for the Src-like adapter protein SLAP-2 in signaling by the colony stimulating factor-1 receptor.
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pubmed:affiliation |
Department of Medicine and Cooperative Research Centre for Chronic Inflammatory Diseases, The University of Melbourne, Royal Melbourne Hospital, Victoria, Australia.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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