The type I TGF-beta receptor is covalently modified and regulated by sumoylation.
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-beta (TGF-beta) receptor, T beta RI, is sumoylated in response to TGF-beta and that its sumoylation requires the kinase activities of both T beta RI and the type II TGF-beta receptor, T beta RII. Sumoylation of T beta RI enhances receptor function by facilitating the recruitment and phosphorylation of Smad3, consequently regulating TGF-beta-induced transcription and growth inhibition. T beta RI sumoylation modulates the dissemination of transformed cells in a mouse model of T beta RI-stimulated metastasis. T beta RI sumoylation therefore controls responsiveness to TGF-beta, with implications for tumour progression. Sumoylation of cell-surface receptors may regulate other growth factor responses.
Kang
Jong Seok
JS
Department of Cell and Tissue Biology, Program in Cell Biology, University of California - San Francisco, California 94143, USA.
Saunier
Elise F
EF
Akhurst
Rosemary J
RJ
Derynck
Rik
R
D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D003593:Cytoplasm / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D008239:Lysine / Q000737:chemistry; D051379:Mice; D008954:Models, Biological; D009362:Neoplasm Metastasis; D010766:Phosphorylation; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism / Q000502:physiology*; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism / Q000502:physiology*; D025842:SUMO-1 Protein / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism
D018125:Receptors, Transforming Growth Factor beta; D025842:SUMO-1 Protein; D016212:Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; D008239:Lysine