Complementation between kinase-defective and activation-defective TGF-β receptors reveals a novel form of receptor cooperativity essential for signaling Journal Article

   

Authors:	Weis-Garcia, F.; Massagué, J.
Article Title:	Complementation between kinase-defective and activation-defective TGF-β receptors reveals a novel form of receptor cooperativity essential for signaling
Abstract:	Transforming growth factor-β (TGF-β) signals through two transmembrane serine/threonine kinases, TβR-I and TβR-II. TGF-β binds to TβR-II, allowing this receptor to associate with and phosphorylate TβR-I which then propagates the signal. TβR-I is phosphorylated within its GS domain, a region immediately preceding the kinase domain. To further understand the function of TβR-I in this complex, we analyzed TβR-I-inactivating mutations identified in cell lines that are defective in TGF-β signaling yet retain ligand binding ability. The three mutations identified here all fall in the kinase domain of TβR-I. One mutation disrupts the kinase activity of TβR-I, whereas the other two mutations prevent ligand-induced TβR-I phosphorylation, and thus activation, by TβR-II. Unexpectedly, a kinase-defective TβR-I mutant can functionally complement an activation-defective TβR-I mutant, by rescuing its TβR-II-dependent phosphorylation. Together with evidence that the ligand-induced receptor complex contains two or more TβR-I molecules, these results support a model in which the kinase domain of one TβR-I molecule interacts with the GS domain of another, enabling its phosphorylation and activation by TβR-II. This cooperative interaction between TβR-I molecules appears essential for TGF-β signal transduction.
Keywords:	signal transduction; controlled study; protein phosphorylation; gene mutation; mutation; sequence deletion; nonhuman; mutant protein; polymerase chain reaction; protein domain; animal cell; animals; cell line; enzyme activity; transfection; protein serine threonine kinase; animalia; amino acid sequence; conserved sequence; molecular sequence data; sequence homology, amino acid; protein-serine-threonine kinases; membrane protein; transforming growth factor; transforming growth factor beta receptor; receptors, transforming growth factor beta; binding sites; point mutation; ligand binding; protein structure, secondary; receptor binding; cell mutant; macromolecular substances; northern blotting; tetradecanoylphorbol acetate; receptor subtype; genetic complementation test; cooperativity; humans; priority journal; article; serine-threonine kinase; models, structural; tgf-β receptors
Journal Title:	EMBO Journal
Volume:	15
Issue:	2
ISSN:	0261-4189
Publisher:	Wiley Blackwell
Date Published:	1996-01-15
Start Page:	276
End Page:	289
Language:	English
PUBMED:	8617203
PROVIDER:	scopus
PMCID:	PMC449943
DOI:	10.1002/j.1460-2075.1996.tb00358.x
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-0030030373&partnerID=40&md5=b0472221f5b4f436ec0566bcf50f5c7e
Notes:	Article -- Export Date: 22 November 2017 -- Source: Scopus

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