Protein Kinase C (PKC) activation "resuces" the endocytosis defect of the Y348A-mutated α1B-adrenergic receptor (α1BAR)

Myron Lee Toews, J. L. Anderson, L. Wang, J. Wang

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Abstract

We reported previously that mutation of Tyr348 of the hamster α1BAR to Ala and expression in CHO cells generated a receptor (Y348A) that undergoes agonist-induced "sequestration" within the plasma membrane, assessed as a decrease in [3H]prazosin binding to intact cells on ice, but not "endocytosis" into intracellular vesicles, assessed as a shift of receptors to the light vesicle fraction on sucrose density gradients [Mol. Pharmacol 52:306, 1997]. We tested whether the PKC activator phorbol 12-myristate 13-acetate (PMA) together with agonist might restore endocytosis to the Y348A α1BAR, based on the requirement for PMA plus agonist for endocytosis of the endogenous α1BAR in DDT1 MF-2 hamster smooth muscle cells [Mol. Pharmacol. 34:340, 1988]. PMA alone induced little sequestration or endocytosis of the Y348A receptor, but PMA together with the agonist epinephrine induced sequestration and endocytosis similar to that induced by agonist alone for the wild-type receptor. These results indicate that PKC activation can "rescue" the endocytosis defect of the Y348A α1BAR, perhaps analagous to the rescue of the sequestration defect of the Y326A β2AR by overexpression of β-adrenergic receptor kinase [J. Biol. Chem. 270:24782, 1995].

Original languageEnglish (US)
JournalFASEB Journal
Volume12
Issue number5
StatePublished - Mar 20 1998

Fingerprint

adrenergic receptors
protein kinase C
endocytosis
Endocytosis
Adrenergic Receptors
Protein Kinase C
agonists
Chemical activation
Acetates
Defects
acetates
receptors
hamsters
Cricetinae
Prazosin
Ice
Cell membranes
CHO Cells
Epinephrine
epinephrine

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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Protein Kinase C (PKC) activation "resuces" the endocytosis defect of the Y348A-mutated α1B-adrenergic receptor (α1BAR). / Toews, Myron Lee; Anderson, J. L.; Wang, L.; Wang, J.

In: FASEB Journal, Vol. 12, No. 5, 20.03.1998.

Research output: Contribution to journalArticle

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