Transforming growth factor β receptor signaling and endocytosis are linked through a COOH terminal activation motif in the type I receptor

N. Garamszegi, Jr Doré, S. G. Penheiter, M. Edens, D. Yao, E. B. Leof

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

Transforming growth factor β (TGF-β) coordinates a number of biological events important in normal and pathophysiological growth. In this study, deletion and substitution mutations were used to identify receptor motifs modulating TGF-β receptor activity. Initial experiments indicated that a COOH-terminal sequence between amino acids 482-491 in the kinase domain of the type I receptor was required for ligand-induced receptor signaling and down-regulation. These 10 amino acids are highly conserved in mammalian, Xenopus, and Drosophila type I receptors. Although mutation or deletion of the region (referred to as the NANDOR BOX, for nonactivating non-down-regulating) abolishes TGF-β-dependent mitogenesis, transcriptional activity, type I receptor phosphorylation, and down-regulation in mesenchymal cultures, adjacent mutations also within the kinase domain are without effect. Moreover, a kinase-defective type I receptor can functionally complement a mutant BOX expressing type I receptor, documenting that when the BOX mutant is activated, it has kinase activity. These results indicate that the sequence between 482 and 491 in the type I receptor provides a critical function regulating activation of the TGF-β receptor complex.

Original languageEnglish (US)
Pages (from-to)2881-2893
Number of pages13
JournalMolecular biology of the cell
Volume12
Issue number9
DOIs
StatePublished - Jan 1 2001

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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