The atypical kinase Cdk5 is activated by insulin, regulates the association between GLUT4 and E-Syt1, and modulates glucose transport in 3T3-L1 adipocytes.
Here, we report that Cdk5 activation is stimulated by insulin and plays a key role in the regulation of GLUT4-mediated glucose uptake in 3T3-L1 adipocytes. Insulin activation of Cdk5 requires PI3K signaling. Insulin-activated Cdk5 phosphorylates E-Syt1, a 5 C2-domain protein-related to the synaptotagmins that is induced during adipocyte differentiation. Phosphorylated E-Syt1 associates with GLUT4, an event inhibited by the Cdks inhibitor roscovitine. Cdk5 silencing inhibits glucose uptake by 3T3-L1 adipocytes. These studies elucidate a previously unknown activity of Cdk5 and demonstrate the involvement of this kinase in the regulation of insulin-dependent glucose uptake in adipocytes.
Lalioti
Vasiliki
V
Department of Cell Biology and Immunology, Centro de Biologia Molecular Severo Ochoa, Universidad Autónoma de Madrid, 28049 Madrid, Spain.
Muruais
Gemma
G
Dinarina
Ana
A
van Damme
Josef
J
Vandekerckhove
Joel
J
Sandoval
Ignacio V
IV
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport; D002135:Calcium-Binding Proteins; D051360:Cyclin-Dependent Kinase 5 / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000378:metabolism*; D007328:Insulin / Q000502:physiology*; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation
D002135:Calcium-Binding Proteins; C539617:E-Syt1 protein, mouse; C534722:E-Syt2 protein, mouse; D051275:Glucose Transporter Type 4; D007328:Insulin; D008565:Membrane Proteins; C495693:Slc2a4 protein, mouse; D019869:Phosphatidylinositol 3-Kinases; D051360:Cyclin-Dependent Kinase 5; C495906:Cdk5 protein, mouse; D005947:Glucose