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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1995 Feb 28;92(5):1565–1569. doi: 10.1073/pnas.92.5.1565

Biochemical evidence for the autophosphorylation and transphosphorylation of transforming growth factor beta receptor kinases.

F Chen 1, R A Weinberg 1
PMCID: PMC42560  PMID: 7878020

Abstract

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 pathways. 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-1 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 over-expression, 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.

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Selected References

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