生物
信号转导
SOCS3
造血
细胞因子信号抑制因子
细胞因子
斯达
贾纳斯激酶
细胞生物学
SH2域
基因剔除小鼠
车站3
免疫学
受体
遗传学
酪氨酸激酶
干细胞
作者
Warren S. Alexander,Robyn Starr,Donald Metcalf,Sandra E. Nicholson,Alison Farley,Andrew G. Elefanty,Marta Brysha,Benjamin T. Kile,Rachel Richardson,Manuel Baca,Jian Guo Zhang,Tracy A. Willson,Elizabeth M. Viney,Naomi S. Sprigg,Steven Rakar,Jason Corbin,Sandra Mifsud,Ladina DiRago,Dale Cary,Nicos A. Nicola,Douglas J. Hilton
摘要
SOCS-1 was originally identified as an inhibitor of interleukin-6 signal transduction and is a member of a family of proteins (SOCS-1 to SOCS-7 and CIS) that contain an SH2 domain and a conserved carboxyl-terminal SOCS box motif. Mutation studies have established that critical contributions from both the amino-terminal and SH2 domains are essential for SOCS-1 and SOCS-3 to inhibit cytokine signaling. Inhibition of cytokine-dependent activation of STAT3 occurred in cells expressing either SOCS-1 or SOCS-3, but unlike SOCS-1, SOCS-3 did not directly interact with or inhibit the activity of JAK kinases. Although the conserved SOCS box motif appeared to be dispensable for SOCS-1 and SOCS-3 action when overexpressed, this domain interacts with elongin proteins and may be important in regulating protein turnover. In gene knockout studies, SOCS-1(-/-) mice were born but failed to thrive and died within 3 weeks of age with fatty degeneration of the liver and hemopoietic infiltration of several organs. The thymus in SOCS-1(-/-) mice was small, the animals were lymphopenic, and deficiencies in B lymphocytes were evident within hemopoietic organs. We propose that the absence of SOCS-1 in these mice prevents lymphocytes and liver cells from appropriately controlling signals from cytokines with cytotoxic side effects.
科研通智能强力驱动
Strongly Powered by AbleSci AI