Tyrosine phosphorylation of the c-cbl proto-oncogene product mediated by cell surface antigen CD38 in HL-60 cells.
The human cell surface antigen CD38 is a 46-kDa type II transmembrane glycoprotein with a short N-terminal cytoplasmic domain and a long Cys-rich C-terminal extracellular one. We demonstrated previously that the extracellular domain of CD38 has NAD+ glycohydrolase (NADase) activity and that the ecto-form NADase activity induced in HL-60 cells during cell differentiation by retinoic acid is due to CD38. In the present study, we investigated the intracellular signaling mediated by CD38 in retinoic acid-differentiated HL-60 cells with an anti-CD38 monoclonal antibody. The addition of anti-CD38 monoclonal antibody to the cells induced rapid tyrosine phosphorylation of the cellular proteins with molecular weights of 120,000, 87,000, and 77,000. An increase in tyrosine kinase activity in the anti-phosphotyrosine immunoprecipitates of the cells was also observed after the addition of anti-CD38 monoclonal antibody. Moreover, one of the prominent tyrosine-phosphorylated proteins stimulated by the anti-CD38 monoclonal antibody was identified as the c-cbl proto-oncogene product, p120c-cbl. These results indicated that tyrosine phosphorylation of cellular proteins, including p120c-cbl, is possibly involved in transmembrane signaling mediated by CD38.
Kontani
K
K
Department of Physiological Chemistry, Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.
Kukimoto
I
I
Nishina
H
H
Hoshino
S
S
Hazeki
O
O
Kanaho
Y
Y
Katada
T
T
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism*; D000943:Antigens, Differentiation / Q000276:immunology / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D007700:Kinetics; D008562:Membrane Glycoproteins; D009699:N-Glycosyl Hydrolases / Q000276:immunology / Q000378:metabolism*; D009244:NAD+ Nucleosidase / Q000378:metabolism*; D010750:Phosphoproteins / Q000302:isolation & purification / Q000378:metabolism; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000032:analysis / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000302:isolation & purification / Q000378:metabolism*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000302:isolation & purification / Q000378:metabolism*; D050721:Proto-Oncogene Proteins c-cbl; D014212:Tretinoin / Q000494:pharmacology; D044767:Ubiquitin-Protein Ligases
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; C000715470:MAS1 protein, human; D008562:Membrane Glycoproteins; D010750:Phosphoproteins; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D019000:Phosphotyrosine; D014212:Tretinoin; D050721:Proto-Oncogene Proteins c-cbl; D044767:Ubiquitin-Protein Ligases; D011505:Protein-Tyrosine Kinases; D009699:N-Glycosyl Hydrolases; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D009244:NAD+ Nucleosidase; D051997:ADP-ribosyl Cyclase 1; C067419:CBL protein, human