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HMG-I(Y) phosphorylation status as a nuclear target regulated through insulin receptor substrate-1 and the I4R motif of the interleukin-4 receptor.

Wang D, Zamorano J, Keegan AD, Boothby M
J Biol Chem. 1997 272 (40): 25083-90

PMID: 9312117 · DOI:10.1074/jbc.272.40.25083

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 alpha chain (IL-4Ralpha). The I4R is a tyrosine-containing motif within IL-4Ralpha 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-1-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 HMG-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.

MeSH Terms (27)

Androstadienes Animals Antigens, CD Cell Nucleus Cells, Cultured Enzyme Induction Enzyme Inhibitors Hematopoietic Stem Cells High Mobility Group Proteins HMGA1a Protein Humans Insulin Receptor Substrate Proteins Macromolecular Substances Mutagenesis, Site-Directed Phosphoproteins Phosphorylation Point Mutation Rats Receptors, Interleukin Receptors, Interleukin-4 Recombinant Proteins Signal Transduction STAT6 Transcription Factor Trans-Activators Transfection Tyrosine Wortmannin

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