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Internalization-Dependent and -Independent Requirements for Transforming Growth Factor β Receptor Signaling via the Smad Pathway

Penheiter, Sumedha G., Mitchell, Hugh, Garamszegi, Nandor, Edens, Maryanne, Doré, Jules J. E., Leof, Edward B.·2002·Molecular and Cellular Biology
DOI 10.1128/mcb.22.13.4750-4759.2002
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Abstract

Members of the transforming growth factor beta (TGF-beta) family of proteins signal through cell surface transmembrane serine/threonine protein kinases known as type I and type II receptors. The TGF-beta signal is extended through phosphorylation of receptor-associated Smad proteins by the type I receptor. Although numerous investigations have established the sequence of events in TGF-beta receptor (TGF-beta R) activation, none have examined the role of the endocytic pathway in initiation and/or maintenance of the signaling response. In this study we investigated whether TGF-beta R internalization modulates type I receptor activation, the formation of a functional receptor/Smad/SARA complex, Smad2/3 phosphorylation or nuclear translocation, and TGF-beta-dependent reporter gene activity. Our data provide evidence that, whereas type I receptor phosphorylation and association of SARA and Smad2 with the TGF-beta R complex take place independently of clathrin lattice formation, Smad2 or Smad3 activation and downstream signaling only occur after endocytic vesicle formation. Thus, TGF-beta R endocytosis is not simply a way to dampen the signaling response but instead is required to propagate signaling via the Smad pathway.

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  • Smad2 and Smad3 activation by liganded TGF-beta receptors occurs only post-endocytic internalization.

    “Intriguingly, Smad2 and Smad3 activation by liganded TGF-b receptors occurs only post-endocytic internalization (Penheiter et al., 2002), raising the possibility that Dab2, acting at the coated vesicle, coordinates aspects of TGF-b signaling.”

    From Disabled‐2 exhibits the properties of a cargo‐selective endocytic clathrin adaptor (2002) · cites this paper as Penheiter et al., 2002

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Metadata

Authors
Penheiter, S. G., Mitchell, H., Garamszegi, N., Edens, M., Doré, J. J. E., & Leof, E. B.
Venue
Molecular and Cellular Biology
Publisher
Informa UK Limited
Published
2002-07-01
Volume
22
Issue
13
Pages
4750-4759
ISSN
1098-5549
DOI
10.1128/mcb.22.13.4750-4759.2002
Cited by
167
References
0
Language
en
Licence
journals.asm.org/non-commercial-tdm-license (tdm)

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