cAMP-dependent protein kinase enhances inositol 1,4,5-trisphosphate-induced Ca2+ release in AR4-2J cells

✍ Scribed by Yannik Regimbald-Dumas; Guillaume Arguin; Marc-Olivier Fregeau; Gaétan Guillemette

• Publisher: John Wiley and Sons
• Year: 2007
• Tongue: English
• Weight: 276 KB
• Volume: 101
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/jcb.21221

✦ Synopsis

Abstract

In non‐excitable cells, the inositol 1,4,5‐trisphosphate receptor (IP~3~R), a ligand‐gated Ca^2+^ channel, plays an important role in the control of intracellular Ca^2+^. There are three subtypes of IP~3~R that are differentially distributed among cell types. AR4‐2J cells express almost exclusively the IP~3~R‐2 subtype. The purpose of this study was to investigate the effect of cAMP‐dependent protein kinase (PKA) on the activity of IP~3~R‐2 in AR4‐2J cells. We showed that immunoprecipitated IP~3~R‐2 is a good substrate for PKA. Using a back‐phosphorylation approach, we showed that endogenous PKA phosphorylates IP~3~R‐2 in intact AR4‐2J cells. Pretreatment with PKA enhanced IP~3~‐induced Ca^2+^ release in permeabilized AR4‐2J cells. Pretreatment with the cAMP generating agent's forskolin and vasoactive intestinal peptide (VIP) enhanced carbachol (Cch)‐induced and epidermal growth factor (EGF)‐induced Ca^2+^ responses in intact AR4‐2J cells. Our results are consistent with an enhancing effect of PKA on IP~3~R‐2 activity. This conclusion supports the emerging concept of crosstalk between Ca^2+^ signaling and cAMP pathways and thus provides another way by which Ca^2+^ signals are finely encoded within non‐excitable cells. J. Cell. Biochem. 101: 609–618, 2007. © 2007 Wiley‐Liss, Inc.