@article{6cb5ba0a3d2e443f9e90236d571aea3a,
title = "The erythropoietin receptor cytosolic juxtamembrane domain contains an essential, precisely oriented, hydrophobic motif",
abstract = "We report that the erythropoietin receptor cytosolic juxtamembrane region is conformationally rigid and contains a hydrophobic motif, composed of residues L253, I257, and W258, 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 L253 is contained within an α helix functionally continuous to the transmembrane α helix. The α-helical orientation of L253 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.",
author = "Constantinescu, {Stefan N.} and Huang, {Lily Jun shen} and Nam, {Hyung song} and Lodish, {Harvey F.}",
note = "Funding Information: We thank Dr. Mike Root for stimulating discussions and advice on insertional mutagenesis and coiled-coil geometry; Dr. Xuedong Liu for critical reading of the manuscript and sharing reagents; Drs. Merav Socolovsky, Pete Carr, and Steve Johnston for critical comments and suggestions; Drs. William Russ and Donald M. Engelman for advice; Stream Wang for excellent technical assistance; and Glenn Paradis, MIT/CCR Central Flow Cytometry Laboratory, for invaluable help with FACS sorting and analysis. This research is supported by grant HL 32262 from the National Institutes of Health and by a grant to H. F. L. from Amgen Corporation. S. N. C. held fellowships from the Anna Fuller Fund and The Medical Foundation/Charles A. King Trust. L. J. H. holds a postdoctoral fellowship from the National Institutes of Health.",
year = "2001",
doi = "10.1016/S1097-2765(01)00185-X",
language = "English (US)",
volume = "7",
pages = "377--385",
journal = "Molecular cell",
issn = "1097-2765",
publisher = "Cell Press",
number = "2",
}