TY - JOUR
T1 - IL-4 and IL-13 receptor signaling from 4PS to insulin receptor substrate 2
T2 - There and back again, a historical view
AU - Keegan, Achsah D.
AU - Zamorano, Jose
AU - Keselman, Aleksander
AU - Heller, Nicola M.
N1 - Funding Information:
First and foremost, we acknowledge the many contributions of Bill Paul to the initial discovery and characterization of 4PS and IRS control of IL-4-induced responses, and for providing mentoring and guidance for studies spanning the past 28 years. We further acknowledge the many NIH colleagues including Jacalyn H. Pierce, Ling-Mei Wang, Keats Nelms, John J. Ryan, Cyndy Watson, Jane Hu-Li, Carol Adler, Warren Leonard, and John J. O'Shea who provided expertise and critical input to the effort. We also acknowledge members of our laboratories who contributed directly to 4PS/IRS projects including Helen Wang, Li Li, Ann Kelly-Welch, Greg Carey, Holly Porter, Preeta Dasgupta, Nicolas Dorsey, Xiulan Qi, Sarah McCormick, and Kristi Warren. Finally, we acknowledge the many other investigators in the field whose work continues to illuminate the complex role of IRS family members in the regulation of allergic disease. This work was supported by the National Institutes of Health awards R56AI122631 (ADK) and R01HL124477 (NH), the United States Veteran's Administration Merit Award I01 BX001850 (ADK), and the Junta de Extremadura (Spain) GR15115 (JZ).
Publisher Copyright:
© 2018 Keegan, Zamorano, Keselman and Heller.
PY - 2018/5/15
Y1 - 2018/5/15
N2 - In this historical perspective, written in honor of Dr. William E. Paul, we describe the initial discovery of one of the dominant substrates for tyrosine phosphorylation stimulated by IL-4. We further describe how this "IL-4-induced phosphorylated substrate" (4PS) was characterized as a member of the insulin receptor substrate (IRS) family of large adaptor proteins that link IL-4 and insulin receptors to activation of the phosphatidyl-inositol 3' kinase pathway as well as other downstream signaling pathways. The relative contribution of the 4PS/IRS pathway to the early models of IL-4-induced proliferation and suppression of apoptosis are compared to our more recent understanding of the complex interplay between positive and negative regulatory pathways emanating from members of the IRS family that impact allergic responses.
AB - In this historical perspective, written in honor of Dr. William E. Paul, we describe the initial discovery of one of the dominant substrates for tyrosine phosphorylation stimulated by IL-4. We further describe how this "IL-4-induced phosphorylated substrate" (4PS) was characterized as a member of the insulin receptor substrate (IRS) family of large adaptor proteins that link IL-4 and insulin receptors to activation of the phosphatidyl-inositol 3' kinase pathway as well as other downstream signaling pathways. The relative contribution of the 4PS/IRS pathway to the early models of IL-4-induced proliferation and suppression of apoptosis are compared to our more recent understanding of the complex interplay between positive and negative regulatory pathways emanating from members of the IRS family that impact allergic responses.
KW - Allergy
KW - IL-4-induced phosphorylated substrate
KW - Insulin receptor substrate
KW - Interleukin-13
KW - Interleukin-13 receptor alpha1 subunit
KW - Interleukin-4
KW - Interleukin-4 receptor a
KW - Macrophage activation
UR - http://www.scopus.com/inward/record.url?scp=85047003271&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85047003271&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2018.01037
DO - 10.3389/fimmu.2018.01037
M3 - Review article
C2 - 29868002
AN - SCOPUS:85047003271
SN - 1664-3224
VL - 9
JO - Frontiers in immunology
JF - Frontiers in immunology
IS - MAY
M1 - 1037
ER -