Definition of the role of tyrosine residues of the common beta subunit regulating multiple signaling pathways of granulocyte-macrophage colony-stimulating factor receptor.

Molecular and Cellular Biology
T ItohS Watanabe

Abstract

Granulocyte-macrophage colony-stimulating factor (GM-CSF) induces various functions, including the proliferation and differentiation of a broad range of hematopoietic cells. We previously reported that at least two distinct pathways are involved in human GM-CSF receptor signaling; both require the box 1 region of the common beta subunit (beta c). This region is essential for the activation of JAK2, which is necessary for all the biological functions of GM-CSF. The activation of JAK2 by GM-CSF leads to rapid tyrosine phosphorylation of cellular proteins, including the beta c. However, the significance of beta c phosphorylation with regard to the regulation of signaling molecules and the expression of GM-CSF functions is less well understood. Here we investigated the role of the cytoplasmic tyrosine residues of the beta c by using a series of beta c mutants expressed in murine BA/F3 cells. A mutant beta c with all eight cytoplasmic tyrosines converted to phenylalanine (Fall) activated JAK2 but not SHP-2, MAPK cascades, STAT5, or the c-fos promoter in BA/F3 cells, and it did not effectively induce proliferation. Adding back each tyrosine to Fall revealed that Tyr577, Tyr612, and Tyr695 are involved in the activation of SHP-2, MAPK...Continue Reading

References

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Citations

Mar 22, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·S WatanabeK Arai
Dec 21, 2000·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Y SakuraiS Watanabe
Dec 17, 2003·Current Opinion in Hematology·Marco TartagliaMignon L Loh
May 3, 2005·Cancer Immunology, Immunotherapy : CII·Naïma MazouzMichel Toungouz
Jan 20, 2012·Growth Factors·Timothy R HercusAngel F Lopez
Nov 2, 2005·Pediatric Blood & Cancer·Jennifer O LauchleKevin Shannon
Feb 17, 2010·Cellular and Molecular Life Sciences : CMLS·Gabriela BrumattiPaul G Ekert
Jan 12, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Larissa M LiontosC Jane McGlade
Jul 16, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Taizo MoriSatoshi Takaki
Jun 13, 2000·Oncogene·J HerringtonC Carter-Su
Sep 13, 2000·Molecular and Cellular Biology·H GuB G Neel
May 10, 2001·International Journal of Hematology·C J BagleyA F Lopez
Apr 24, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Rong ZengSumiko Watanabe
Jul 1, 2005·Expert Review of Clinical Immunology·Magdalena M Gorska, Rafeul Alam
Apr 9, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Kathleen M Sakamoto, David A Frank
Jul 11, 2000·The Journal of Allergy and Clinical Immunology·R LiuS Watanabe
Nov 28, 2002·Biochimie·Sumiko WatanabeKen-ichi Arai
Dec 31, 2002·Biochemical and Biophysical Research Communications·Eiji AkagawaSumiko Watanabe

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