Association of phosphatidylinositol 3-kinase with the proto-oncogene product Cbl upon CD38 ligation by a specific monoclonal antibody in THP-1 cells.

We reported that ecto-NAD+ glycohydrolase activity induced upon differentiation of HL-60 cells with retinoic acid is localized on the extracellular domain of CD38 and that CD38 ligation by a specific monoclonal antibody, HB-7, is followed by rapid tyrosine phosphorylation of cellular proteins including a proto-oncogene product, Cbl. In the present ...
study, we investigated intracellular signaling linked to the HB-7-induced Cbl phosphorylation in dibutyryl cAMP-treated THP-1 cells. The 85-kDa regulatory subunit (p85) of phosphatidylinositol (PI) 3-kinase was immunoprecipitated with anti-Cbl antibody in a manner dependent on the tyrosine phosphorylation of Cbl. PI 3-kinase activity was also observed in the immunoprecipitated fractions containing tyrosine-phosphorylated Cbl. The phosphorylated form of Cbl, which had been separated from the CD38-stimulated cells, was capable of directly binding to a recombinant p85 fused to glutathione S-transferase. Thus, the direct association of tyrosine-phosphorylated Cbl with PI 3-kinase, possibly leading to the kinase activation, appeared to be involved in intracellular signaling caused by the CD38 ligation.
Mesh Terms:
ADP-ribosyl Cyclase, Antibodies, Monoclonal, Antigens, CD, Antigens, CD38, Antigens, Differentiation, Bucladesine, Humans, Immunoblotting, Membrane Glycoproteins, Monocytes, N-Glycosyl Hydrolases, Phosphatidylinositol 3-Kinases, Phosphorylation, Phosphotransferases (Alcohol Group Acceptor), Phosphotyrosine, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-cbl, Recombinant Fusion Proteins, Signal Transduction, Tumor Cells, Cultured, Ubiquitin-Protein Ligases, src Homology Domains
FEBS Lett.
Date: Nov. 11, 1996
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