Journal article
JAK2 associates with the beta c chain of the receptor for granulocyte-macrophage colony-stimulating factor, and its activation requires the membrane-proximal region
Molecular and cellular biology, Vol.14(7), pp.4335-4341
07/1994
DOI: 10.1128/mcb.14.7.4335-4341.1994
PMCID: PMC358804
PMID: 8007942
Abstract
The high-affinity receptor for granulocyte-macrophage colony-stimulating factor (GM-CSF) consists of a unique alpha chain and a beta c subunit that is shared with the receptors for interleukin-3 (IL-3) and IL-5. Two regions of the beta c chain have been defined; these include a membrane-proximal region of the cytoplasmic domain that is required for mitogenesis and a membrane-distal region that is required for activation of Ras, Raf-1, mitogen-activated protein kinase, and S6 kinase. Recent studies have implicated the cytoplasmic protein tyrosine kinase JAK2 in signalling through a number of the cytokine receptors, including the IL-3 and erythropoietin receptors. In the studies described here, we demonstrate that GM-CSF stimulation of cells induces the tyrosine phosphorylation of JAK2 and activates its in vitro kinase activity. Mutational analysis of the beta c chain demonstrates that only the membrane-proximal 62 amino acids of the cytosolic domain are required for JAK2 activation. Thus, JAK2 activation is correlated with induction of mitogenesis but does not, alone, activate the Ras pathway. Carboxyl truncations of the alpha chain, which inactivate the receptor for mitogenesis, are unable to mediate GM-CSF-induced JAK2 activation. Using baculovirus-expressed proteins, we further demonstrate that JAK2 physically associates with the beta c chain but not with the alpha chain. Together, the results further support the hypothesis that the JAK family of kinase are critical to coupling cytokine binding to tyrosine phosphorylation and ultimately mitogenesis.
Details
- Title: Subtitle
- JAK2 associates with the beta c chain of the receptor for granulocyte-macrophage colony-stimulating factor, and its activation requires the membrane-proximal region
- Creators
- Frederick W Quelle - Department of Biochemistry, St. Jude Children's Research Hospital, Memphis, Tennessee 38105Noriko SatoBruce A Witthuhn - Department of Biochemistry, St. Jude Children's Research Hospital, Memphis, Tennessee 38105Roger C Inhorn - Dana-Farber Cancer InstituteMatthias Eder - Dana-Farber Cancer InstituteAtsushi MiyajimaJames D Griffin - Dana-Farber Cancer InstituteJames N Ihle - University of Tennessee Health Science Center
- Resource Type
- Journal article
- Publication Details
- Molecular and cellular biology, Vol.14(7), pp.4335-4341
- DOI
- 10.1128/mcb.14.7.4335-4341.1994
- PMID
- 8007942
- PMCID
- PMC358804
- ISSN
- 0270-7306
- eISSN
- 1098-5549
- Language
- English
- Date published
- 07/1994
- Academic Unit
- Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984040535102771
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