TY - JOUR
T1 - HMG-I(Y) phosphorylation status as a nuclear target regulated through insulin receptor substrate-1 and the I4R motif of the interleukin-4 receptor
AU - Wang, Dingzhi
AU - Zamorano, Jose
AU - Keegan, Achsah D.
AU - Boothby, Mark
N1 - Copyright:
Copyright 2007 Elsevier B.V., All rights reserved.
PY - 1997/10/3
Y1 - 1997/10/3
N2 - Interleukin (IL)-4 is a cytokine that regulates both the growth and differentiation of hematopoietic cells. Its ligand binding specificity and important signal transduction mechanisms are conferred by the IL-4 receptor α chain (IL-4Rα). The I4R is a tyrosine-containing motif within IL-4Rα that is critical for proliferative responses to IL-4. Although the I4R also contributes to gene regulation, nuclear targets directly regulated by this motif have not been described. It is shown here that the tyrosine at position 497 in the I4R is critical for regulation of the phosphorylation status of a set of nuclear proteins that includes HMG-I(Y), small non-histone chromosomal proteins involved in the control of gene expression in hematopoietic cell lines. Moreover, IL-4 is unable to induce HMG-I(Y) phosphorylation in insulin receptor substrate-l-deficient cells, and the inhibitor wortmannin completely blocks IL-4 regulation of HMG-I(Y) phosphorylation status but not activation of an IL-4 Stat protein. Taken together, these data indicate that HMC-I(Y) is a nuclear target whose phosphorylation status is regulated through the I4R motif via insulin receptor substrate proteins, independent of activation of the Stat pathway.
AB - Interleukin (IL)-4 is a cytokine that regulates both the growth and differentiation of hematopoietic cells. Its ligand binding specificity and important signal transduction mechanisms are conferred by the IL-4 receptor α chain (IL-4Rα). The I4R is a tyrosine-containing motif within IL-4Rα that is critical for proliferative responses to IL-4. Although the I4R also contributes to gene regulation, nuclear targets directly regulated by this motif have not been described. It is shown here that the tyrosine at position 497 in the I4R is critical for regulation of the phosphorylation status of a set of nuclear proteins that includes HMG-I(Y), small non-histone chromosomal proteins involved in the control of gene expression in hematopoietic cell lines. Moreover, IL-4 is unable to induce HMG-I(Y) phosphorylation in insulin receptor substrate-l-deficient cells, and the inhibitor wortmannin completely blocks IL-4 regulation of HMG-I(Y) phosphorylation status but not activation of an IL-4 Stat protein. Taken together, these data indicate that HMC-I(Y) is a nuclear target whose phosphorylation status is regulated through the I4R motif via insulin receptor substrate proteins, independent of activation of the Stat pathway.
UR - http://www.scopus.com/inward/record.url?scp=0030820812&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0030820812&partnerID=8YFLogxK
U2 - 10.1074/jbc.272.40.25083
DO - 10.1074/jbc.272.40.25083
M3 - Article
C2 - 9312117
AN - SCOPUS:0030820812
SN - 0021-9258
VL - 272
SP - 25083
EP - 25090
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 40
ER -