PubMed:16623714
Annnotations
{"target":"https://pubannotation.org/docs/sourcedb/PubMed/sourceid/16623714","sourcedb":"PubMed","sourceid":"16623714","source_url":"http://www.ncbi.nlm.nih.gov/pubmed/16623714","text":"A potential role for the Src-like adapter protein SLAP-2 in signaling by the colony stimulating factor-1 receptor.\nThe 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.","tracks":[{"project":"AnEM_abstracts","denotations":[{"id":"T1","span":{"begin":134,"end":145},"obj":"Cell"},{"id":"T2","span":{"begin":151,"end":175},"obj":"Cell"},{"id":"T3","span":{"begin":285,"end":298},"obj":"Cellular_component"},{"id":"T4","span":{"begin":404,"end":409},"obj":"Cell"},{"id":"T5","span":{"begin":607,"end":618},"obj":"Multi-tissue_structure"},{"id":"T6","span":{"begin":627,"end":638},"obj":"Cell"},{"id":"T7","span":{"begin":711,"end":734},"obj":"Cell"},{"id":"T8","span":{"begin":1136,"end":1159},"obj":"Cell"}],"attributes":[{"subj":"T1","pred":"source","obj":"AnEM_abstracts"},{"subj":"T2","pred":"source","obj":"AnEM_abstracts"},{"subj":"T3","pred":"source","obj":"AnEM_abstracts"},{"subj":"T4","pred":"source","obj":"AnEM_abstracts"},{"subj":"T5","pred":"source","obj":"AnEM_abstracts"},{"subj":"T6","pred":"source","obj":"AnEM_abstracts"},{"subj":"T7","pred":"source","obj":"AnEM_abstracts"},{"subj":"T8","pred":"source","obj":"AnEM_abstracts"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"AnEM_abstracts","color":"#ec93dc","default":true}]}]}}