Losman J A, Chen X P, Hilton D, Rothman P
Integrated Program in Molecular, Cellular, and Biophysical Studies, Department of Medicine, Columbia University, College of Physicians and Surgeons, New York 10032, USA.
J Immunol. 1999 Apr 1;162(7):3770-4.
IL-4 is an important regulator of the activation, proliferation, and differentiation of many hematopoetic cells. Many of these biological effects result from the activation of Janus kinases (JAK)1 and JAK3 and the transcription factor Stat6. Recent data suggest that members of the SOCS (suppressor of cytokine signaling) family of proteins can inhibit JAK-STAT signaling. We have examined the ability of SOCS family members to suppress IL-4 signaling, and we have found that SOCS-1 potently inhibits the activation of JAK1 kinase and Stat6 in response to IL-4. Furthermore, SOCS-1 can inhibit the induction of CD23 expression by IL-4. SOCS-2 does not inhibit induction of signaling by IL-4, while inhibition of IL-4 signaling by SOCS-3 can be detected in transient transfection systems, but not in stable cell lines. These studies implicate SOCS-1 in modulation of IL-4 signaling and suggest that SOCS-1 may play a role in regulating the immune response.
白细胞介素-4是多种造血细胞激活、增殖和分化的重要调节因子。这些生物学效应中的许多是由Janus激酶(JAK)1和JAK3以及转录因子Stat6的激活所导致的。最近的数据表明,细胞因子信号转导抑制因子(SOCS)蛋白家族的成员可以抑制JAK-STAT信号传导。我们已经研究了SOCS家族成员抑制白细胞介素-4信号传导的能力,并且发现SOCS-1能有效抑制JAK1激酶和Stat6对白细胞介素-4的应答激活。此外,SOCS-1可以抑制白细胞介素-4诱导的CD23表达。SOCS-2不抑制白细胞介素-4诱导的信号传导,而在瞬时转染系统中可以检测到SOCS-3对白细胞介素-4信号传导的抑制作用,但在稳定细胞系中则检测不到。这些研究表明SOCS-1参与白细胞介素-4信号传导的调节,并提示SOCS-1可能在调节免疫反应中发挥作用。