| First Author | Sharma P | Year | 2008 |
| Journal | Immunity | Volume | 29 |
| Issue | 4 | Pages | 551-64 |
| PubMed ID | 18957266 | Mgi Jnum | J:140644 |
| Mgi Id | MGI:3814259 | Doi | 10.1016/j.immuni.2008.07.019 |
| Citation | Sharma P, et al. (2008) Redox regulation of interleukin-4 signaling. Immunity 29(4):551-64 |
| abstractText | 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-alpha, 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. |
