Specific association of phosphatidylinositol 3-kinase with the protooncogene product Cbl in Fc gamma receptor signaling.
A tyrosine-phosphorylated protein with a molecular mass of 115 kDa was reported to be tightly associated with the p85 regulatory subunit of phosphatidylinositol (PI) 3-kinase, when the enzyme was essentially activated upon ligand engagement of Fc gamma receptors (Fc gamma R) leading to engulfment of IgG-coated erythrocytes by phagocytes [Ninomiya et al. (1994) J. Biol. Chem. 269, 22732-22737]. Here, the 115-kDa protein is identified as the product of human c-cbl protooncogene. Cross-linking of Fc gamma RII on the surface of THP-1 cells triggered (a) prominent tyrosine phosphorylation of Cbl, (b) activation of PI 3-kinase that was immunoprecipitated with the anti-Cbl or the anti-phosphotyrosine antibody, and (c) specific association of Cbl with p85. Thus, Cbl functions in phagocytes as a result of its association with PI 3-kinase in response to Fc gamma R ligation.
Matsuo
T
T
Ui Laboratory, Institute of Physical and Chemical Research, Wako-shi, Japan.
Hazeki
K
K
Hazeki
O
O
Katada
T
T
Ui
M
M
D000911:Antibodies, Monoclonal; D002460:Cell Line; D003432:Cross-Linking Reagents; D004789:Enzyme Activation; D006801:Humans; D009000:Monocytes / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases; D010766:Phosphorylation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D019000:Phosphotyrosine / Q000032:analysis; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D050721:Proto-Oncogene Proteins c-cbl; D017452:Receptors, IgG / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D044767:Ubiquitin-Protein Ligases
D000911:Antibodies, Monoclonal; D003432:Cross-Linking Reagents; D011518:Proto-Oncogene Proteins; D017452:Receptors, IgG; D019000:Phosphotyrosine; D050721:Proto-Oncogene Proteins c-cbl; D044767:Ubiquitin-Protein Ligases; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); C067419:CBL protein, human