TY - JOUR
T1 - The N-terminal domain of Janus kinase 2 is required for golgi processing and cell surface expression of erythropoietin receptor
AU - Huang, Lily Jun shen
AU - Constantinescu, Stefan N.
AU - Lodish, Harvey F.
N1 - Funding Information:
We thank Drs. Xiaoxia Li and George Stark (Cleveland Clinic Foundation, Cleveland, OH) for providing us with γ2A cell line; Dr. Joe Avruch (Massachusetts General Hospital) for providing the pEBG expression vector; Dr. Chang-Zheng Chen for providing the vector expressing GST-fused cytoplasmic domain of EpoR; Dr. Saghi Ghaffari for providing JAK2-deficient mouse embryos; Dr. James Ihle (St. Jude Children's Research Hospital) for providing expression vectors of JAK1 and JAK2; Glenn Paradis (MIT/CCR Central Flow Cytometry Laboratory) for invaluable help with FACS sorting and analysis; Char DeCroos and Yohan Royer for excellent technical assistance; and Drs. J. Bogan, N. Chi, S. Johnston, D. Neumann, C. Rodriguez, and M. Socolovsky for helpful discussions and critical reading of the manuscript. 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. L.J.H. holds a postdoctoral fellowship from the National Institutes of Health. S.N.C. held fellowships from the Anna Fuller Fund and the Medical Foundation/Charles A. King Trust.
PY - 2001
Y1 - 2001
N2 - We show that Janus kinase 2 (JAK2), and more specifically just its intact N-terminal domain, binds to the erythropoietin receptor (EpoR) in the endoplasmic reticulum and promotes its cell surface expression. This interaction is specific as JAK1 has no effect. Residues 32 to 58 of the JAK2 JH7 domain are required for EpoR surface expression. Alanine scanning mutagenesis of the EpoR membrane proximal region reveals two modes of EpoR-JAK2 interaction. A continuous block of EpoR residues is required for functional, ligand-independent binding to JAK2 and cell surface receptor expression, whereas four specific residues are essential in switching on prebound JAK2 after ligand binding. Thus, in addition to its kinase activity required for cytokine receptor signaling, JAK is also an essential subunit required for surface expression of cytokine receptors.
AB - We show that Janus kinase 2 (JAK2), and more specifically just its intact N-terminal domain, binds to the erythropoietin receptor (EpoR) in the endoplasmic reticulum and promotes its cell surface expression. This interaction is specific as JAK1 has no effect. Residues 32 to 58 of the JAK2 JH7 domain are required for EpoR surface expression. Alanine scanning mutagenesis of the EpoR membrane proximal region reveals two modes of EpoR-JAK2 interaction. A continuous block of EpoR residues is required for functional, ligand-independent binding to JAK2 and cell surface receptor expression, whereas four specific residues are essential in switching on prebound JAK2 after ligand binding. Thus, in addition to its kinase activity required for cytokine receptor signaling, JAK is also an essential subunit required for surface expression of cytokine receptors.
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U2 - 10.1016/S1097-2765(01)00401-4
DO - 10.1016/S1097-2765(01)00401-4
M3 - Article
C2 - 11779507
AN - SCOPUS:0035694582
SN - 1097-2765
VL - 8
SP - 1327
EP - 1338
JO - Molecular cell
JF - Molecular cell
IS - 6
ER -