Journal
MOLECULAR CELL
Volume 7, Issue 2, Pages 377-385Publisher
CELL PRESS
DOI: 10.1016/S1097-2765(01)00185-X
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- NHLBI NIH HHS [HL 32262] Funding Source: Medline
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We report that the erythropoietin receptor cytosolic juxtamembrane region is conformationally rigid and contains a hydrophobic motif, composed of residues L-253, I-257, and W-258, that is crucial for Janus kinase 2 (JAK2) activation and receptor signaling. Alanine insertion mutagenesis shows that the orientation of this motif and not its distance from the membrane bilayer is critical. Intragenic complementation studies suggest that L-253 is contained within an alpha helix functionally continuous to the transmembrane alpha helix. The alpha -helical orientation of L-253 is required not for JAK2 activation but for activated JAK2 to induce phosphorylation of the erythropoietin receptor. This motif is highly conserved among cytokine receptors and couples ligand-induced conformational changes in the receptor to intracellular activation of JAK2.
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