Faculty Collaboration Database

A Protein Kinase C Phosphorylation Motif in GLUT1 Affects Glucose Transport and is Mutated in GLUT1 Deficiency Syndrome. Mol Cell 2015 Jun 04;58(5):845-53

Date

05/20/2015

Pubmed ID

25982116

Pubmed Central ID

PMC4458224

DOI

10.1016/j.molcel.2015.04.015

Scopus ID

2-s2.0-84940053942 (requires institutional sign-in at Scopus site)   88 Citations

Abstract

Protein kinase C has been implicated in the phosphorylation of the erythrocyte/brain glucose transporter, GLUT1, without a clear understanding of the site(s) of phosphorylation and the possible effects on glucose transport. Through in vitro kinase assays, mass spectrometry, and phosphospecific antibodies, we identify serine 226 in GLUT1 as a PKC phosphorylation site. Phosphorylation of S226 is required for the rapid increase in glucose uptake and enhanced cell surface localization of GLUT1 induced by the phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate (TPA). Endogenous GLUT1 is phosphorylated on S226 in primary endothelial cells in response to TPA or VEGF. Several naturally occurring, pathogenic mutations that cause GLUT1 deficiency syndrome disrupt this PKC phosphomotif, impair the phosphorylation of S226 in vitro, and block TPA-mediated increases in glucose uptake. We demonstrate that the phosphorylation of GLUT1 on S226 regulates glucose transport and propose that this modification is important in the physiological regulation of glucose transport.

Author List

Lee EE, Ma J, Sacharidou A, Mi W, Salato VK, Nguyen N, Jiang Y, Pascual JM, North PE, Shaul PW, Mettlen M, Wang RC

Author

Paula E. North MD, PhD Professor in the Pathology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Amino Acid Sequence
Animals
Biological Transport
Carbohydrate Metabolism, Inborn Errors
Cell Line
Endothelial Cells
Erythrocytes
Glucose
Glucose Transporter Type 1
HeLa Cells
Humans
Molecular Sequence Data
Monosaccharide Transport Proteins
Mutation, Missense
Phosphorylation
Protein Kinase C-alpha
Protein Processing, Post-Translational
Rats
Xenopus laevis