Open AccessTyrosine phosphorylation is a mandatory proximal step in radiation-induced activation of the protein kinase C signaling pathway in human B-lymphocyte precursors.
Author(s) -
Fatih M. Uckun,
Gary L. Schieven,
Lisa TuelAhlgren,
İlker Dıbırdık,
Dorothea E. Myers,
Jeffrey A. Ledbetter,
Chang W. Song
Publication year - 1993
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.90.1.252
Subject(s) - tyrosine phosphorylation , phosphorylation , signal transduction , tyrosine kinase , protein tyrosine phosphatase , microbiology and biotechnology , protein kinase c , biology , receptor tyrosine kinase , tyrosine , ask1 , biochemistry , chemistry , cancer research , mitogen activated protein kinase kinase
Ionizing radiation triggers a signal in human B-lymphocyte precursors that is intimately linked to an active protein-tyrosine kinase regulatory pathway. We show that in B-lymphocyte precursors, irradiation with gamma-rays leads to (i) stimulation of phosphatidylinositol turnover; (ii) downstream activation by covalent modification of multiple serine-specific protein kinases, including protein kinase C; and (iii) activation of nuclear factor kappa B. All of the radiation-induced signals were effectively prevented by the protein-tyrosine kinase inhibitors genistein and herbimycin A. Thus, tyrosine phosphorylation is an important and perhaps mandatory proximal step in the activation of the protein kinase C signaling cascade in human B-lymphocyte precursors. Our report expands current knowledge of the radiation-induced signaling cascade by clarifying the chronological sequence of biochemical events that follow irradiation.