Effects of second messengers on serine/threonine protein phosphatases in insulin-secreting cells

Åke Sjöholm, Per Olof Berggren, Richard E. Honkanen

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


Reversible protein phosphorylation is an important and versatile mechanism by which cells transduce external signals into biological responses. Cellular levels of protein phosphorylation are determined by the balanced actions of both protein kinases and protein phosphatases (PPases). Compared with protein kinases, however, serine/threonine PPases have received less attention. In the present study, the effects of certain insulin secretagogues and intracellular second messengers, known to stimulate or inhibit insulin secretion, on the activities of cation-independent serine/threonine PPases were investigated in insulin-secreting RINm5F insulinoma cells. Raising cellular cAMP through adenylyl cyclase activation and phosphodiesterase inhibition in intact cells, evoked inhibitory effects on PPase activities. The addition of a nitric oxide donor, cyclic nucleotides, or proinflammatory prostaglandins to RINm5F cell homogenates at widely different concentrations did not affect type-1 or -2A PPase activities. Phosphatidyl serine seemingly activated PPase-1, while inactivating PPase-2A. A protein kinase C-activating phorbol ester produced the opposite results when added to RINm5F cell homogenates. These studies suggest that several known intracellular second messengers are without effect on β-cell PPase activities. However, phosphatidyl serine and protein kinase C activation, whose activity is transiently increased by glucose, may promote insulin release through PPase inactivation, likely contributing to the increase in phosphorylation state that occurs after stimulation of insulin release. Thus, inhibition of protein dephosphorylation may be a novel regulatory mechanism, assisting in activation of the stimulus-secretion coupling in insulin-producing cells.

Original languageEnglish (US)
Pages (from-to)364-368
Number of pages5
JournalBiochemical and biophysical research communications
Issue number2
StatePublished - 2001

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


Dive into the research topics of 'Effects of second messengers on serine/threonine protein phosphatases in insulin-secreting cells'. Together they form a unique fingerprint.

Cite this