Association of cyclin-dependent kinase-4 and cyclin D1 in neonatal beta cells after mitogenic stimulation by lysophosphatidic acid.
Neonatal pancreatic islet beta cells retain a mitogenic capacity in response to growth factors. In this study an increased incorporation of 5-bromo-2'-deoxyuridine in response to oleoyl-lysophosphatidic acid is preceded by a GTP-dependent increase in phosphorylation of the extracellular signal-related kinase, ERK1. The presence of cyclin-dependent kinase-4 and an association with a catalytic partner cyclin D1, a process by which the progression through the cell cycle is regulated in other cell types, was shown to follow this. The mechanisms linking ERK1 phosphorylation and activation of cell cycle progression are not known. Investigation of this process in neonatal beta cells may provide a common pathway for the early response to growth factors and the conditions required for an increase in beta cell mass by proliferation.
Dunlop
M
M
University of Melbourne, Department of Medicine, Royal Melbourne Hospital, Parkville, Victoria, Australia.
Muggli
E
E
Clark
S
S
D000818:Animals; D000831:Animals, Newborn; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002478:Cells, Cultured; D019938:Cyclin D1; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases / Q000096:biosynthesis* / Q000302:isolation & purification; D016213:Cyclins / Q000096:biosynthesis*; D004247:DNA / Q000096:biosynthesis; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008246:Lysophospholipids / Q000494:pharmacology*; D008715:Methionine / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D008934:Mitogens / Q000494:pharmacology*; D015513:Oncogene Proteins / Q000096:biosynthesis*; D010766:Phosphorylation; D011518:Proto-Oncogene Proteins; D051381:Rats; D013462:Sulfur Radioisotopes
D016213:Cyclins; D008246:Lysophospholipids; D008934:Mitogens; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D013462:Sulfur Radioisotopes; D019938:Cyclin D1; D004247:DNA; D008715:Methionine; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C495903:Cdk4 protein, rat; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases