Regulation of GLUT1-mediated glucose uptake by PKClambda-PKCbeta(II) interactions in 3T3-L1 adipocytes.
Members of the PKC (protein kinase C) superfamily play key regulatory roles in glucose transport. How the different PKC isotypes are involved in the regulation of glucose transport is still poorly defined. PMA is a potent activator of conventional and novel PKCs and PMA increases the rate of glucose uptake in many different cell systems. In the present study, we show that PMA treatment increases glucose uptake in 3T3-L1 adipocytes by two mechanisms: a mitogen-activated protein kinase kinase-dependent increase in GLUT1 (glucose transporter 1) expression levels and a PKClambda-dependent translocation of GLUT1 towards the plasma membrane. Intriguingly, PKClambda co-immunoprecipitated with PKCbeta(II) and did not with PKCbeta(I). Previously, we have described that down-regulation of PKCbeta(II) protein levels or inhibiting PKCbeta(II) by means of the myristoylated PKCbetaC2-4 peptide inhibitor induced GLUT1 translocation towards the plasma membrane in 3T3-L1 adipocytes. Combined with the present findings, these results suggest that the liberation of PKClambda from PKCbeta(II) is an important factor in the regulation of GLUT1 distribution in 3T3-L1 adipocytes.
Bosch
Remko R
RR
Department of Chemical Endocrinology, University Medical Centre Nijmegen, Nijmegen, The Netherlands. R.R.Bosch@vet.uu.nl
Bazuine
Merlijn
M
Span
Paul N
PN
Willems
Peter H G M
PH
Olthaar
André J
AJ
van Rennes
Helga
H
Maassen
J Antonie
JA
Tack
Cees J
CJ
Hermus
Ad R M M
AR
Sweep
C G J Fred
CG
D041721:3T3-L1 Cells / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D017667:Adipocytes / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D004789:Enzyme Activation / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism*; D051272:Glucose Transporter Type 1; D047468:Immunoprecipitation / Q000379:methods; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors / Q000502:physiology; D008969:Molecular Sequence Data; D009004:Monosaccharide Transport Proteins / Q000096:biosynthesis / Q000378:metabolism*; D019814:Myristic Acid / Q000378:metabolism; D010455:Peptides / Q000037:antagonists & inhibitors / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D064546:Protein Kinase C beta; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D000099293:Protein Kinase C-lambda
D004791:Enzyme Inhibitors; D005947:Glucose; D051272:Glucose Transporter Type 1; D007527:Isoenzymes; D020929:Mitogen-Activated Protein Kinase Kinases; D009004:Monosaccharide Transport Proteins; D019814:Myristic Acid; D010455:Peptides; D011493:Protein Kinase C; D064546:Protein Kinase C beta; D013755:Tetradecanoylphorbol Acetate; D000099293:Protein Kinase C-lambda; C495678:Slc2a1 protein, mouse