Constitutive activation of the thyrotropin receptor by mutating CYS-636 in the sixth transmembrane segment.

Abstract:

:The rat thyrotropin receptor (TSHR) has 7 Cys residues in its transmembrane (TM) segments. We investigated the roles of these Cys residues by individually mutating each to Ser, transfecting the mutant DNA into Cos-7 cells and measuring TSH binding and cAMP/phosphoinositide (PIP2) responses to TSH and Graves' IgGs. Mutation of Cys-636 in the 6th TM helix to Ser markedly increased cAMP level without stimulation. Constitutive activation by this mutation contributes to a more complete map for activating TSHR mutation. Mutation of other Cys residues partially impaired responses but no mutants showed complete loss of receptor function, indicating that these residues have no major contribution to the overall 3-D structure of the TSHR.

authors

Kosugi S,Mori T

doi

10.1006/bbrc.1996.0809

subject

Has Abstract

pub_date

1996-05-24 00:00:00

pages

713-7

issue

3

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(96)90809-8

journal_volume

222

pub_type

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