DARPP-32 and inhibitor-1 are expressed in pancreatic beta-cells.
Insulin secretion from pancreatic beta-cells has to be tightly regulated to ensure accurate glucose homeostasis. The capacity of beta-cells to respond to extracellular stimulation is determined by several signaling pathways. One important feature of these pathways is phosphorylation and subsequent dephosphorylation of a wide range of cellular substrates. Protein phosphatase 1 (PP1) is a major eukaryotic serine/threonine protein phosphatase that controls a multitude of physiological processes. We have investigated the expression and cellular distribution of two endogenous inhibitors of PP1 activity in beta-cells. RT-PCR, Western blotting, and immunohistochemistry showed that DARPP-32 and inhibitor-1 are present in insulin-secreting endocrine beta-cells. Subcellular fractionation of mouse islets revealed that both PP1 inhibitors predominantly localized to cytosol-enriched fractions. Inhibitor-1 was also present in fractions containing plasma membrane-associated proteins. These data indicate a potential role for DARPP-32 and inhibitor-1 in the regulation of PP1 activity in pancreatic beta-cell stimulus-secretion coupling.
Lilja
Lena
L
The Rolf Luft Center for Diabetes Research, Department of Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, SE-171 76 Stockholm, Sweden.
Meister
Björn
B
Berggren
Per-Olof
PO
Bark
Christina
C
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism*; D002478:Cells, Cultured; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D007328:Insulin / Q000378:metabolism*; D007515:Islets of Langerhans / Q000378:metabolism*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors*; D010750:Phosphoproteins / Q000378:metabolism*; D054645:Protein Phosphatase 1; D011506:Proteins / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism*
D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D007328:Insulin; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; D011506:Proteins; C073882:phosphoprotein phosphatase inhibitor 1; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1