Article abstract
Nature Cell Biology 10, 654 - 664 (2008)
Published online: 11 May 2008 | doi:10.1038/ncb1728
The type I TGF-
receptor is covalently modified and regulated by sumoylation
Jong Seok Kang1, Elise F. Saunier2, Rosemary J. Akhurst2,3,4 & Rik Derynck1,3
Abstract
Post-translational sumoylation, the covalent attachment of a small ubiquitin-like modifier (SUMO), regulates the functions of proteins engaged in diverse processes. Often associated with nuclear and perinuclear proteins, such as transcription factors, it is not known whether SUMO can conjugate to cell-surface receptors for growth factors to regulate their functions. Here we show that the type I transforming growth factor-
(TGF-) receptor, TRI, is sumoylated in response to TGF- and that its sumoylation requires the kinase activities of both TRI and the type II TGF- receptor, TRII. Sumoylation of TRI enhances receptor function by facilitating the recruitment and phosphorylation of Smad3, consequently regulating TGF--induced transcription and growth inhibition. TRI sumoylation modulates the dissemination of transformed cells in a mouse model of TRI-stimulated metastasis. TRI sumoylation therefore controls responsiveness to TGF-, with implications for tumour progression. Sumoylation of cell-surface receptors may regulate other growth factor responses.
- Department of Cell and Tissue Biology, Program in Cell Biology, University of California – San Francisco, San Francisco, California 94143, USA.
- Cancer Research Institute, University of California – San Francisco, San Francisco, California 94143, USA.
- Department of Anatomy, University of California – San Francisco, San Francisco, California 94143, USA.
- Program In Human Genetics, University of California – San Francisco, San Francisco, California 94143, USA.
Correspondence to: Rik Derynck1,3 e-mail: rik.derynck@ucsf.edu
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