Identification of a functional site on the type I TGF-beta receptor by mutational analysis of its ectodomain.

Abstract:

:Six charged amino acid residues located in the ectodomain of the full-length type I transforming growth factor (TGF)-beta receptor were individually mutated to alanine. Mutation of residues D47, D98, K102 and E104 resulted in functionally impaired receptors as demonstrated by a marked decrease in ligand-dependent signaling and ligand internalization relative to the wild-type receptor. The other two mutants (K39A and K87A) exhibited wild-type-like activity. Molecular modeling indicates that the four functionally important residues are located on the convex face of the ectodomain structure. Since mutation of these four residues affects signaling and ligand internalization but not ligand binding, we propose that this functional site is an interacting site between type I and II receptors.

journal_name

FEBS Lett

journal_title

FEBS letters

authors

Guimond A,Sulea T,Zwaagstra JC,Ekiel I,O'Connor-McCourt MD

doi

10.1016/s0014-5793(01)03231-8

keywords:

subject

Has Abstract

pub_date

2002-02-27 00:00:00

pages

147-52

issue

2-3

eissn

0014-5793

issn

1873-3468

pii

S0014579301032318

journal_volume

513

pub_type

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