Identification of the major tyrosine kinase substrate in signaling complexes formed after engagement of Fc gamma receptors.
We have recently identified the protein product of the c-cbl proto-oncogene as an SH3 binding protein expressed in macrophages. To investigate the possibility that p120c-cbl is involved in signaling pathways initiated by cell surface receptors for IgG (Fc gamma R), lysates of HL60 cells were examined for tyrosine phosphorylation of p120c-cbl upon Fc gamma R engagement. Our findings demonstrate that p120c-cbl is tyrosine-phosphorylated upon Fc gamma R engagement and that this molecule represents the major tyrosine kinase substrate in this signaling pathway. Protein complexes containing p120c-cbl, p72syk, and p56lyn were observed either in resting or activated cells. In vitro studies showed that the direct association between p120c-cbl and p56lyn was mediated by the SH3 domain of p56lyn.
Marcilla
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A
Laboratory of Cellular Development and Oncology, NIDR, National Institutes of Health, Bethesda, Maryland 20892-4330, USA.
Rivero-Lezcano
O M
OM
Agarwal
A
A
Robbins
K C
KC
D004792:Enzyme Precursors / Q000502:physiology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D050721:Proto-Oncogene Proteins c-cbl; D017452:Receptors, IgG / Q000502:physiology*; D000072377:Syk Kinase; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases; D019061:src-Family Kinases
D004792:Enzyme Precursors; D047908:Intracellular Signaling Peptides and Proteins; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D017452:Receptors, IgG; D014443:Tyrosine; D050721:Proto-Oncogene Proteins c-cbl; D044767:Ubiquitin-Protein Ligases; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases; C067419:CBL protein, human