ERK3 associates with MAP2 and is involved in glucose-induced insulin secretion.
The adaptation of pancreatic islets to pregnancy includes increased beta cell proliferation, expansion of islet mass, and increased insulin synthesis and secretion. Most of these adaptations are induced by prolactin (PRL). We have previously described that in vitro PRL treatment increases ERK3 expression in isolated rat pancreatic islets. This study shows that ERK3 is also upregulated during pregnancy. Islets from pregnant rats treated with antisense oligonucleotide targeted to the PRL receptor displayed a significant reduction in ERK3 expression. Immunohistochemical double-staining showed that ERK3 expression is restricted to pancreatic beta cells. Transfection with antisense oligonucleotide targeted to ERK3 abolished the insulin secretion stimulated by glucose in rat islets and by PMA in RINm5F cells. Therefore, we examined the participation of ERK3 in the activation of a cellular target involved in secretory events, the microtubule associated protein MAP2. PMA induced ERK3 phosphorylation that was companied by an increase in ERK3/MAP2 association and MAP2 phosphorylation. These observations provide evidence that ERK3 is involved in the regulation of stimulus-secretion coupling in pancreatic beta cells.
Anhê
Gabriel F
GF
Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, USP, 05508-900 São Paulo, Brazil.
Torrão
Andréa S
AS
Nogueira
Tatiane C A
TC
Caperuto
Luciana C
LC
Amaral
Maria E C
ME
Medina
Mayrin C
MC
Azevedo-Martins
Anna K
AK
Carpinelli
Angelo R
AR
Carvalho
Carla R O
CR
Curi
Rui
R
Boschero
Antonio C
AC
Bordin
Silvana
S
D000818:Animals; D002478:Cells, Cultured; D005260:Female; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D048053:Mitogen-Activated Protein Kinase 6 / Q000096:biosynthesis*; D023421:Models, Animal; D016376:Oligonucleotides, Antisense; D010766:Phosphorylation; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D011981:Receptors, Prolactin / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015854:Up-Regulation
D007328:Insulin; D008869:Microtubule-Associated Proteins; D016376:Oligonucleotides, Antisense; D011981:Receptors, Prolactin; D048053:Mitogen-Activated Protein Kinase 6; D005947:Glucose; D013755:Tetradecanoylphorbol Acetate