Role of Syk in Fcγ receptor-coupled tyrosine phosphorylation of Cbl in a manner susceptible to inhibition by protein kinase C

Kaoru Hazeki, Osamu Hazeki, Tsuyoshi Matsuo, Tsukasa Seya, Toshiyuki Yamashita, Shigeharu Nagasawa, Hamid Band, Michio Ui

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Fcγ receptors (FcγR) of guinea pig neutrophils were ligated and anti-Cbl immunoprecipitates prepared therefrom were assayed for the associated protein tyrosine kinase activity, which increased upon ligation of FcγR. The increases were overcome upon activation of cellular protein kinase C by simultaneous addition of phorbol 12-myristate 13-acetate (PMA) to the ligated cells. Syk proved to be the most important tyrosine kinase bound to Cbl that served as the major substrate; essentially no tyrosine phosphorylation occurred in the anti-Cbl immunoprecipitates prepared from the cell lysate that had been depleted of Syk by prior immunoprecipitation with anti-Syk antibodies. Exposure of the 32P-labeled cells to PMA resulted in phosphorylation of cellular Cbl on serine residues. Thus, protein kinase C-induced serine phosphorylation of Cbl suppressed its tyrosine phosphorylation by Syk as a result of tyrosine kinase inhibition by unknown mechanisms, leading to inhibition of Cbl-mediated signaling such as phosphatidylinositol 3-kinase activation.

Original languageEnglish (US)
Pages (from-to)3302-3312
Number of pages11
JournalEuropean Journal of Immunology
Volume29
Issue number10
DOIs
StatePublished - Oct 26 1999

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Fc Receptors
Protein Kinase C
Tyrosine
Phosphorylation
Protein-Tyrosine Kinases
Serine
Acetates
Phosphatidylinositol 3-Kinase
Immunoprecipitation
Ligation
Anti-Idiotypic Antibodies
Guinea Pigs
Neutrophils
phorbol-12-myristate

Keywords

  • Cbl
  • Fcγ receptor
  • Protein kinase C
  • Syk
  • Tyrosine phosphorylation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Role of Syk in Fcγ receptor-coupled tyrosine phosphorylation of Cbl in a manner susceptible to inhibition by protein kinase C. / Hazeki, Kaoru; Hazeki, Osamu; Matsuo, Tsuyoshi; Seya, Tsukasa; Yamashita, Toshiyuki; Nagasawa, Shigeharu; Band, Hamid; Ui, Michio.

In: European Journal of Immunology, Vol. 29, No. 10, 26.10.1999, p. 3302-3312.

Research output: Contribution to journalArticle

Hazeki, Kaoru ; Hazeki, Osamu ; Matsuo, Tsuyoshi ; Seya, Tsukasa ; Yamashita, Toshiyuki ; Nagasawa, Shigeharu ; Band, Hamid ; Ui, Michio. / Role of Syk in Fcγ receptor-coupled tyrosine phosphorylation of Cbl in a manner susceptible to inhibition by protein kinase C. In: European Journal of Immunology. 1999 ; Vol. 29, No. 10. pp. 3302-3312.
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AU - Seya, Tsukasa

AU - Yamashita, Toshiyuki

AU - Nagasawa, Shigeharu

AU - Band, Hamid

AU - Ui, Michio

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