Skip to Main content Skip to Navigation
Journal articles

ERK1/2 control phosphorylation and protein level of cAMP-responsive element-binding protein: a key role in glucose-mediated pancreatic beta-cell survival.

Abstract : cAMP-responsive element-binding protein (CREB) is required for beta-cell survival by regulating expression of crucial genes such as bcl-2 and IRS-2. Using MIN6 cells and isolated rat pancreatic islets, we investigated the signaling pathway that controls phosphorylation and protein level of CREB. We observed that 10 mmol/l glucose-induced CREB phosphorylation was totally inhibited by the protein kinase A (PKA) inhibitor H89 (2 micromol/l) and reduced by 50% with the extracellular signal-regulated kinase (ERK)1/2 inhibitor PD98059 (20 micromol/l). This indicates that ERK1/2, reported to be located downstream of PKA, participates in the PKA-mediated CREB phosphorylation elicited by glucose. In ERK1/2-downregulated MIN6 cells by siRNA, glucose-stimulated CREB phosphorylation was highly reduced and CREB protein content was decreased by 60%. In MIN6 cells and islets cultured for 24-48 h in optimal glucose concentration (10 mmol/l), which promotes survival, blockade of ERK1/2 activity with PD98059 caused a significant decrease in CREB protein level, whereas CREB mRNA remained unaffected (measured by real-time quantitative PCR). This was associated with loss of bcl-2 mRNA and protein contents, caspase-3 activation, and emergence of ultrastructural apoptotic features detected by electron microscopy. Our results indicate that ERK1 and -2 control the phosphorylation and protein level of CREB and play a key role in glucose-mediated pancreatic beta-cell survival.
Document type :
Journal articles
Complete list of metadata

https://hal.archives-ouvertes.fr/hal-00201283
Contributor : Anne Dominique Lajoix Connect in order to contact the contributor
Submitted on : Thursday, December 27, 2007 - 4:10:35 PM
Last modification on : Tuesday, December 1, 2020 - 10:48:03 AM

Links full text

Identifiers

Collections

Citation

Safia Costes, Christophe Broca, Gyslaine Bertrand, Anne-Dominique Lajoix, Dominique Bataille, et al.. ERK1/2 control phosphorylation and protein level of cAMP-responsive element-binding protein: a key role in glucose-mediated pancreatic beta-cell survival.. Diabetes, American Diabetes Association, 2006, 55 (8), pp.2220-30. ⟨10.2337/db05-1618⟩. ⟨hal-00201283⟩

Share

Metrics

Record views

107