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The Bmx Tyrosine Kinase Induces Activation of the Stat Signaling Pathway, Which Is Specifically Inhibited by Protein Kinase C
Pipsa Saharinen,
Niklas Ekman,
Krista Sarvas,
Peter Parker,
Kari Alitalo, and
Olli Silvennoinen
From the Department of Virology, Haartman Institute, University of Helsinki, Finland; Molecular and Cancer Biology Laboratory, Haartman Institute, University of Helsinki, Finland; Imperial Cancer Research Fund, London, UK; and Institute of Medical Technology, University of Tampere, Finland.
Members of the hematopoietically expressed Tec tyrosine kinase family have an important role in hematopoietic signal transduction, as exemplified by the crucial role of Btk for B-cell differentiation and activation. Although a variety of cell surface receptors have been found to activate Tec tyrosine kinases, the specific signaling pathways and substrate molecules used by Tec kinases are still largely unknown. In this study a Tec family kinase, Bmx, was found to induce activation of the Stat signaling pathway. Bmx induced the tyrosine phosphorylation and DNA binding activity of all the Stat factors tested, including Stat1, Stat3, and Stat5, both in mammalian and insect cells. Bmx also induced transcriptional activation of Stat1- and Stat5-dependent reporter genes. Other cytoplasmic tyrosine kinases, Syk, Fyn, and c-Src, showed no or only weak ability to activate Stat proteins. Expression of Bmx in mammalian cells was found to induce activation of endogenous Stat proteins without activation of endogenous Jak kinases. We further analyzed the Bmx-mediated activation of Stat1, which was found to be regulated by protein kinase C  (PKC) isoform, but not  1,  , or  isoforms, leading to inhibition of Stat1 tyrosine phosphorylation. In conclusion, these studies show that Bmx, a Tec family kinase, can function as an activator of the Stat signaling pathway and identify a role for PKC in the regulation of Bmx signaling.
Blood, Vol. 90 No. 11 (December 1), 1997:
pp. 4341-4353
© 1997 by The American Society of Hematology.
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