BIOCHEMICAL-EVIDENCE FOR THE AUTOPHOSPHORYLATION AND TRANSPHOSPHORYLATION OF TRANSFORMING GROWTH-FACTOR-BETA RECEPTOR KINASES

被引:115
作者
CHEN, F
WEINBERG, RA
机构
[1] WHITEHEAD INST BIOMED RES, CAMBRIDGE, MA 02142 USA
[2] MIT, DEPT BIOL, CAMBRIDGE, MA 02139 USA
关键词
TRANSMEMBRANE SERINE; THREONINE KINASES; PHOSPHORYLATION;
D O I
10.1073/pnas.92.5.1565
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Transforming growth factor beta (TGF-beta) signals through a receptor complex containing the type I (TGF-beta RI) and type II (TGF-beta RII) receptors. We describe here biochemical studies on early events in the TGF-beta signaling pathway. TGF-beta RII is highly phosphorylated when expressed alone in COS-1 cells; its autophosphorylation occurs via an intramolecular (cis) mechanism that is independent of ligand binding. TGF-beta RI is also highly phosphorylated when expressed alone in COS-I cells. Both wild-type TGF-beta RI and a kinase-deficient mutant thereof are transphosphorylated by the coexpressed TGF-beta RII kinase in a ligand-independent fashion in these cells. We propose that the association of TGF-beta RI and TGF-beta RII, induced by ligand binding or overexpression, leads to transphosphorylation of the TGF-beta RI by the TGF-beta RII kinase. This represents a mechanism of activation of receptors distinct from that of tyrosine kinase receptors and may apply to other serine/threonine kinase receptors.
引用
收藏
页码:1565 / 1569
页数:5
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