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PMID: 3526339 Published · ppublish English Journal Article Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Protein kinase C directly phosphorylates the insulin receptor in vitro and reduces its protein-tyrosine kinase activity.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 83 ·No. 16 ·1986-08-00 ·Pages 5822-4

Bollag GE, Roth RA, Beaudoin J, Mochly-Rosen D, Koshland DE

Abstract

The beta subunit of purified insulin receptor is phosphorylated on a serine residue by purified preparations of protein kinase C (ATP: protein phosphotransferase, EC 2.7.1.37). This phosphorylation is inhibited by antibodies to protein kinase C and stimulated by phospholipids, diacylglycerol, and Ca2+. The phosphorylation of the receptor by protein kinase C does not affect its insulin-binding activity but does inhibit by 65% the receptor's intrinsic tyrosine-specific protein kinase activity (ATP: protein-tyrosine O-phosphotransferase, EC 2.7.1.112). These results indicate that activators of protein kinase C, such as phorbol esters, desensitize cells to insulin by direct protein kinase C action on the insulin receptor.

MeSH Terms

Animals Enzyme Activation Insulin/analogs & derivatives,metabolism Kinetics Macromolecular Substances Phosphorylation Protein Kinase C/metabolism Protein-Tyrosine Kinases/metabolism Receptor, Insulin/metabolism

Chemicals

Insulin Macromolecular Substances insulin, iodo- Protein-Tyrosine Kinases Receptor, Insulin Protein Kinase C

Authors & Affiliations

5 authors, click to expand affiliations / ORCID

Bollag G E

Roth R A

Beaudoin J

Mochly-Rosen D

Koshland D E

References (23)

23 references, click to expand

Affinity alteration of insulin receptor induced by a phorbol ester.
Am J Physiol. 1982 Oct;243(4):E319-24 PMID: 6751097
Insulin action is blocked by a monoclonal antibody that inhibits the insulin receptor kinase.
Proc Natl Acad Sci U S A. 1986 Jan;83(2):328-32 PMID: 3455769
Insulin receptor: evidence that it is a protein kinase.
Science. 1983 Jan 21;219(4582):299-301 PMID: 6849137
Inhibition of insulin receptor binding by phorbol esters.
Eur J Biochem. 1982 Dec 15;129(2):389-93 PMID: 6891320
Phorbol esters stimulate the phosphorylation of receptors for insulin and somatomedin C.
Proc Natl Acad Sci U S A. 1983 Oct;80(20):6211-3 PMID: 6312447
Detection and quantification of phosphotyrosine in proteins.
Methods Enzymol. 1983;99:387-402 PMID: 6196603
C-kinase phosphorylates the epidermal growth factor receptor and reduces its epidermal growth factor-stimulated tyrosine protein kinase activity.
J Biol Chem. 1984 Feb 25;259(4):2553-8 PMID: 6321473
The role of protein kinase C in cell surface signal transduction and tumour promotion.
Nature. 1984 Apr 19-25;308(5961):693-8 PMID: 6232463
Association of phorbol ester-induced hyperphosphorylation and reversible regulation of transferrin membrane receptors in HL60 cells.
Proc Natl Acad Sci U S A. 1984 Apr;81(7):2016-20 PMID: 6326098
Decreased autophosphorylation of the insulin receptor-kinase in streptozotocin-diabetic rats.
J Biol Chem. 1984 Nov 25;259(22):14208-16 PMID: 6389544
Purification and characterization of a Ca2+/calmodulin-dependent protein kinase from rat brain.
Biochemistry. 1984 Nov 6;23(23):5495-504 PMID: 6509030
Phorbol esters modulate insulin receptor phosphorylation and insulin action in cultured hepatoma cells.
Proc Natl Acad Sci U S A. 1984 Dec;81(24):7797-801 PMID: 6393128
Cell-surface proteins. At last the insulin receptor.
Nature. 1985 Feb 28-Mar 6;313(6005):740-1 PMID: 3974708
Tumour-promoting phorbol esters increase basal and inhibit insulin-stimulated lipogenesis in rat adipocytes without decreasing insulin binding.
Biochem J. 1985 Jan 15;225(2):523-7 PMID: 3883992
The molecular mechanism of insulin action.
Annu Rev Med. 1985;36:429-51 PMID: 2986528
How insulin resistant are patients with noninsulin-dependent diabetes mellitus?
J Clin Endocrinol Metab. 1985 Jul;61(1):32-6 PMID: 3889039
Insulin receptor tyrosine kinase is defective in skeletal muscle of insulin-resistant obese mice.
Nature. 1985 Jun 20-26;315(6021):676-9 PMID: 3892304
Molecular mechanisms of receptor desensitization using the beta-adrenergic receptor-coupled adenylate cyclase system as a model.
Nature. 1985 Sep 12-18;317(6033):124-9 PMID: 2993919
Phorbol ester inhibition of hormonal induction of tyrosine aminotransferase.
Biochem Biophys Res Commun. 1985 Sep 16;131(2):815-20 PMID: 2864925
Protein kinase C phosphorylates pp60src at a novel site.
Cell. 1985 Oct;42(3):849-57 PMID: 2996780
Autophosphorylation and protein kinase C phosphorylation of the epidermal growth factor receptor. Effect on tyrosine kinase activity and ligand binding affinity.
J Biol Chem. 1985 Nov 25;260(27):14538-46 PMID: 2997213
The molecular basis of communication within the cell.
Sci Am. 1985 Oct;253(4):142-52 PMID: 2999971
Calcium-activated, phospholipid-dependent protein kinase from rat brain. Subcellular distribution, purification, and properties.
J Biol Chem. 1982 Nov 25;257(22):13341-8 PMID: 7142151

Article Info

Journal

Proceedings of the National Academy of Sciences of the United States of America

Abbr.

Proc Natl Acad Sci U S A

ISSN

0027-8424

DOI

10.1073/pnas.83.16.5822

Published

1986-08-00

Pages

5822-4

Language

English

Region

United States

NLM ID

7505876

PMCID

PMC386387

Subset

External Links

PubMed source DOI: 10.1073/pnas.83.16.5822 PMC Full Text View journal details

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Protein kinase C directly phosphorylates the insulin receptor in vitro and reduces its protein-tyrosine kinase activity.

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