A role for the insulin-interleukin (IL)-4 receptor motif of the IL-4 receptor alpha-chain in regulating activation of the insulin receptor substrate 2 and signal transducer and activator of transcription 6 pathways. Analysis by mutagenesis.

The Journal of Biological Chemistry
H Y WangA D Keegan

Abstract

The interleukin (IL)-4 receptor alpha-chain (IL-4Ralpha) contains a sequence motif (488PLVIAGNPAYRSFSD) termed the insulin IL-4 receptor motif (I4R motif). Mutation of the central Tyr497 to Phe blocks the tyrosine phosphorylation of the insulin receptor substrate 1 (IRS1) and diminishes proliferation in response to IL-4. Recent data suggest that the I4R motif encodes binding sites for several protein tyrosine binding (PTB) domain-containing proteins such as IRS1 and Shc and potentially for the Src homology 2 domain of signal transducer and activator of transcription 6 (STAT6). To analyze the function of the I4R motif in regulating IL-4 signaling, we changed conserved residues upstream and downstream of the central Tyr to Ala in the human IL-4Ralpha. We analyzed the ability of these constructs to signal the tyrosine phosphorylation of IRS2 and STAT6, the induction of DNA binding activity, and CD23 induction in response to human IL-4 (huIL-4) in transfected M12.4.1 cells. Mutagenesis of residues downstream of Tyr497, such as Arg498 or Phe500, to Ala had no effect on any of these responses, suggesting that the I4R motif may not be important for functional Src homology 2 domain interactions. However, mutagenesis of Pro488 to Ala (P...Continue Reading

References

Nov 17, 1995·The Journal of Biological Chemistry·G WolfS E Shoelson
Feb 16, 1995·Nature·T Pawson
Mar 10, 1995·Cell·P Bork, B Margolis
Aug 15, 1995·Proceedings of the National Academy of Sciences of the United States of America·A D KeeganW E Paul
Aug 15, 1995·Proceedings of the National Academy of Sciences of the United States of America·A PernisP Rothman
Jul 1, 1995·Trends in Biochemical Sciences·P van der Geer, T Pawson
Jul 18, 1995·Proceedings of the National Academy of Sciences of the United States of America·T G BoultonG D Yancopoulos
Sep 14, 1995·Nature·X J SunM F White
May 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·L M WangS A Aaronson
Feb 1, 1995·Trends in Genetics : TIG·J N Ihle, I M Kerr
Sep 16, 1994·Science·J HouS L McKnight
Mar 1, 1993·Cytokine·D Cosman
Apr 1, 1996·Nature Structural Biology·M M ZhouS W Fesik
Apr 18, 1996·Nature·K TakedaS Akira
Jan 1, 1997·Annual Review of Immunology·E A BachR D Schreiber

❮ Previous
Next ❯

Citations

Jun 8, 1999·Annual Review of Immunology·K NelmsW E Paul
May 19, 2009·American Journal of Physiology. Lung Cellular and Molecular Physiology·Steven R WhiteXiaoying Fu
Feb 3, 2005·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Christine McDonaldNancy C Reich
Jun 16, 2004·Immunological Investigations·Marta Benczik, Sarah L Gaffen
Oct 18, 2000·The Journal of Experimental Medicine·J ZhuW E Paul
Sep 11, 2019·Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology·Hani Harb, Talal A Chatila
Jun 5, 2012·Biomedical Papers of the Medical Faculty of the University Palacký, Olomouc, Czechoslovakia·Marek GodavaRadek Vrtel
Jul 23, 2003·American Journal of Physiology. Lung Cellular and Molecular Physiology·Debora S FaffeStephanie A Shore
Jul 19, 2018·BioMed Research International·Zheng WangXiaoju Zhang
May 1, 2021·Animals : an Open Access Journal From MDPI·Worrarak NorseedaSupamit Mekchay

❮ Previous
Next ❯

Related Concepts

Related Feeds

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.

B-Cell Lymphoma

B-cell lymphomas include lymphomas that affect B cells. This subtype of cancer accounts for over 80% of non-Hodgkin lymphomas in the US. Here is the latest research.