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

FEBS Letters

Matsuo, Tsuyoshi²  Hazeki, Kaoru²  Ui, Michio²  Katada, Toshiaki¹  Tsujimoto, Noriko¹  Inoue, Shin-ichi¹  Kontani, Kenji¹  Kurosu, Hiroshi¹  Hazeki, Osamu¹ 

[1] Department of Physiological Chemistry, Faculty of Pharmaceutical Sciences, University of Tokyo, Tokyo 113, Japan;Ui Laboratory, Institute of Physical and Chemical Research, Wako-shi 351-01, Japan

关键词: CD38;    Phosphatidylinositol 3-kinase;    Proto-oncogene product Cbl;    Tyrosine phosphorylation;    Ab;    antibody;    Bt2;    dibutyryl;    mAb;    monoclonal antibody;    NADase;    NAD+ glycohydrolase;    PI;    phosphatidylinositol;    p85;    85-kDa subunit of PI 3-kinase;    PI-3P;    PI 3-phosphate;    PY;    phosphotyrosine;    GST;    glutathione S-transferase;   

DOI  :  10.1016/S0014-5793(96)01151-9

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown