TY - JOUR
T1 - Redox Regulation of Interleukin-4 Signaling
AU - Sharma, Pankaj
AU - Chakraborty, Rikhia
AU - Wang, Lu
AU - Min, Booki
AU - Tremblay, Michel L.
AU - Kawahara, Tsukasa
AU - Lambeth, J. David
AU - Haque, S. Jaharul
N1 - Funding Information:
We thank T.A. Hamilton, S. Datta, J. Dasgupta, C. Eng, O.I. Stenina, J. Kusari, A. Guha, and J.E. Dixon for sharing of reagents, J.A. Drazba for assistance in imaging, and T. Koeck and K.S. Aulak for technical assistance. We also thank J.A. Houghton, S.C. Erzurum, F.H. Hsieh, G.C. Sen, R.H. Silverman, and B. Raychaudhuri for comments. This work was supported by grants R01 GM060533 and R01 CA095006 from the National Institutes of Health to S.J.H.
PY - 2008/10/17
Y1 - 2008/10/17
N2 - The physiologic control of cytokine receptor activation is primarily mediated by reciprocal activation of receptor-associated protein tyrosine kinases and protein tyrosine phosphatases (PTPs). Here, we show that immediately after ligand-dependent activation, interleukin (IL)-4 receptor generated reactive oxygen species (ROS) via phosphatidylinositol 3-kinase-dependent activation of NAD(P)H oxidase (NOX)1 and NOX5L. ROS, in turn, promoted IL-4 receptor activation by oxidatively inactivating PTP1B that physically associated with and deactivated IL-4 receptor. However, ROS were not required for the initiation of IL-4 receptor activation. ROS generated by other cytokine receptors, including those for erythropoietin, tumor necrosis factor-α, or IL-3, also promoted IL-4 signaling. These data indicate that inactivation of receptor-associated PTP activity by cytokine-generated ROS is a physiologic mechanism for the amplification of cytokine receptor activation in both cis and trans, revealing a role for ROS in cytokine crosstalk.
AB - The physiologic control of cytokine receptor activation is primarily mediated by reciprocal activation of receptor-associated protein tyrosine kinases and protein tyrosine phosphatases (PTPs). Here, we show that immediately after ligand-dependent activation, interleukin (IL)-4 receptor generated reactive oxygen species (ROS) via phosphatidylinositol 3-kinase-dependent activation of NAD(P)H oxidase (NOX)1 and NOX5L. ROS, in turn, promoted IL-4 receptor activation by oxidatively inactivating PTP1B that physically associated with and deactivated IL-4 receptor. However, ROS were not required for the initiation of IL-4 receptor activation. ROS generated by other cytokine receptors, including those for erythropoietin, tumor necrosis factor-α, or IL-3, also promoted IL-4 signaling. These data indicate that inactivation of receptor-associated PTP activity by cytokine-generated ROS is a physiologic mechanism for the amplification of cytokine receptor activation in both cis and trans, revealing a role for ROS in cytokine crosstalk.
KW - MOLIMMUNO
UR - http://www.scopus.com/inward/record.url?scp=53349160071&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=53349160071&partnerID=8YFLogxK
U2 - 10.1016/j.immuni.2008.07.019
DO - 10.1016/j.immuni.2008.07.019
M3 - Article
C2 - 18957266
AN - SCOPUS:53349160071
SN - 1074-7613
VL - 29
SP - 551
EP - 564
JO - Immunity
JF - Immunity
IS - 4
ER -
