JAK2 associates with the β(c) chain of the receptor for granulocyte- macrophage colony-stimulating factor, and its activation requires the membrane-proximal region

F. W. Quelle, N. Sato, B. A. Witthuhn, R. C. Inhorn, M. Eder, A. Miyajima, J. D. Griffin, J. N. Ihle

Research output: Contribution to journalArticlepeer-review

429 Scopus citations

Abstract

The high-affinity receptor for granulocyte-macrophage colony-stimulating factor (GM-CSF) consists of a unique α chain and a β(c) subunit that is shared with the receptors for interleukin-3 (IL-3) and IL-5. Two regions of the β(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 β(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 α 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 β(c) chain but not with the α chain. Together, the results further support the hypothesis that the JAK family of kinases are critical to coupling cytokine binding to tyrosine phosphorylation and ultimately mitogenesis.

Original languageEnglish (US)
Pages (from-to)4335-4341
Number of pages7
JournalMolecular and cellular biology
Volume14
Issue number7
DOIs
StatePublished - 1994

Fingerprint

Dive into the research topics of 'JAK2 associates with the β(c) chain of the receptor for granulocyte- macrophage colony-stimulating factor, and its activation requires the membrane-proximal region'. Together they form a unique fingerprint.

Cite this