The Bmx Tyrosine Kinase Induces Activation of the Stat Signaling Pathway, Which Is Specifically Inhibited by Protein Kinase Cδ

作者: Pipsa Saharinen , Niklas Ekman , Krista Sarvas , Peter Parker , Kari Alitalo

DOI: 10.1182/BLOOD.V90.11.4341

关键词:

摘要: Members of the hematopoietically expressed Tec tyrosine kinase family have an important role in hematopoietic signal transduction, as exemplified by crucial Btk for B-cell differentiation and activation. Although a variety cell surface receptors been found to activate kinases, specific signaling pathways substrate molecules used kinases are still largely unknown. In this study kinase, Bmx, was induce activation Stat pathway. Bmx induced phosphorylation DNA binding activity all factors tested, including Stat1, Stat3, Stat5, both mammalian insect cells. also transcriptional Stat1- Stat5-dependent reporter genes. Other cytoplasmic Syk, Fyn, c-Src, showed no or only weak ability proteins. Expression cells endogenous proteins without Jak kinases. We further analyzed Bmx-mediated which be regulated protein C δ (PKCδ) isoform, but not β 1, e, ζ isoforms, leading inhibition Stat1 phosphorylation. conclusion, these studies show that can function activator pathway identify PKCδ regulation signaling.

参考文章(70)
F Muscatelli, K Alitalo, L Tamagnone, R Alitalo, I Lahtinen, F Francis, C Larsson, T Mustonen, C I E Smith, K Virtaneva, BMX, a novel nonreceptor tyrosine kinase gene of the BTK/ITK/TEC/TXK family located in chromosome Xp22.2. Oncogene. ,vol. 9, pp. 3683- 3688 ,(1994)
A.L. Mui, H. Wakao, A.M. O'Farrell, N. Harada, A. Miyajima, Interleukin-3, granulocyte-macrophage colony stimulating factor and interleukin-5 transduce signals through two STAT5 homologs. The EMBO Journal. ,vol. 14, pp. 1166- 1175 ,(1995) , 10.1002/J.1460-2075.1995.TB07100.X
V Gouilleux-Gruart, F Gouilleux, C Desaint, JF Claisse, JC Capiod, J Delobel, R Weber-Nordt, I Dusanter-Fourt, F Dreyfus, B Groner, L Prin, STAT-related transcription factors are constitutively activated in peripheral blood cells from acute leukemia patients Blood. ,vol. 87, pp. 1692- 1697 ,(1996) , 10.1182/BLOOD.V87.5.1692.1692
RM Weber-Nordt, C Egen, J Wehinger, W Ludwig, V Gouilleux-Gruart, R Mertelsmann, J Finke, Constitutive activation of STAT proteins in primary lymphoid and myeloid leukemia cells and in Epstein-Barr virus (EBV)-related lymphoma cell lines. Blood. ,vol. 88, pp. 809- 816 ,(1996) , 10.1182/BLOOD.V88.3.809.809
Gordon B Mills, T. Kawakami, Y. Kawakami, M. Tashiro, L. Yao, S. Gibson, Activation and interaction with protein kinase C of a cytoplasmic tyrosine kinase, Itk/Tsk/Emt, on FcεRI cross-linking on mast cells Journal of Immunology. ,vol. 155, pp. 3556- 3562 ,(1995)
T. Uchida, T. Matozaki, K. Matsuda, T. Suzuki, S. Matozaki, O. Nakano, K. Wada, Y. Konda, C. Sakamoto, M. Kasuga, Phorbol ester stimulates the activity of a protein tyrosine phosphatase containing SH2 domains (PTP1C) in HL-60 leukemia cells by increasing gene expression. Journal of Biological Chemistry. ,vol. 268, pp. 11845- 11850 ,(1993) , 10.1016/S0021-9258(19)50277-0
D Sliva, T J Wood, C Schindler, P E Lobie, G Norstedt, Growth hormone specifically regulates serine protease inhibitor gene transcription via gamma-activated sequence-like DNA elements. Journal of Biological Chemistry. ,vol. 269, pp. 26208- 26214 ,(1994) , 10.1016/S0021-9258(18)47180-3
D Schaap, P J Parker, Expression, purification, and characterization of protein kinase C-epsilon. Journal of Biological Chemistry. ,vol. 265, pp. 7301- 7307 ,(1990) , 10.1016/S0021-9258(19)39114-8