Cyclic AMP-dependent phosphorylation of a brain inositol trisphosphate receptor decreases its release of calcium.

Abstract

We report the stoichiometric phosphorylation of an inositol 1,4,5-trisphosphate receptor-binding protein from rat brain by the cAMP-dependent protein kinase but not by protein kinase C or Ca2+/calmodulin-dependent protein kinase. This phosphorylation event does not markedly alter [3H]inositol 1,4,5-trisphosphate-binding characteristics. However, inositol 1,4,5-trisphosphate is only 10% as potent in releasing 45Ca2I from phosphorylated, as compared with native, cerebellar microsomes. Phosphorylation of the inositol 1,4,5-trisphosphate-binding protein by the cAMP-dependent protein kinase may provide a biochemical substrate for secondmessenger cross talk.The inositol phospholipid and adenosine 3',5'-cyclic monophosphate (cAMP) systems are major second messengers for effects of neurotransmitters, hormones, and growth factors (1-4). Several lines of evidence imply the existence of cross talk between these two second messengers (5-7). Many

cDNA cloning reveals a tissue specific expression of alternatively spliced transcripts of the ryanodine receptor type 3 (RyR3) calcium release channel

“…The possibility that different combinations of the alternatively spliced variants to form homo-and/or heterotetrameric channels may result in further heterogeneity in the calcium release properties of RyRs. This consideration is further supported by the characterization of the functional properties of the proteins encoded by alternatively spliced transcripts of the InsP3 receptor type 1 [11,24,25].…”

Chronic Lithium Treatment Attenuates Intracellular Calcium Mobilization

“…For example, cAMP-mediated signaling promotes the inhibition of Ca 2 þ influx (Rasmussen, 1986), modulates IP 3 Rs (Supattapone et al, 1988;Patel et al, 1999), and enhances the removal of Ca 2 þ from the cytosol by promoting the action of PMCA pumps (Helman et al, 1986). As well, protein kinase A (PKA) can modulate the PI/Ca 2 þ signaling system through the phosphorylation of several intracellular targets including receptors, G proteins, PI kinase, and phospholipase C (Supattapone et al, 1988;Hajnoczky et al, 1993;Galas and Harden, 1997). Abnormalities of the cAMP-PKA signaling cascade have also been implicated in the pathophysiology of BD and as a target of lithium action (Perez et al, 2000;Chang et al, 2002).…”

A lingering elevation of Cai accompanies inhibition of inositol 1,4,5 trisphosphate-induced Ca release in Limulus ventral photoreceptors.

“…Alternatively, the transient elevation of Cai that immediately follows an injection could trigger an inhibitory mechanism that does not require continued elevation of Cai to sustain its action. A Ca-induced phosphorylation of the InsP3 receptor might, for example, inhibit Ca release (Supattapone, Danoff, Theibert, Joseph, Steiner, and Snyder, 1988). In this article we describe experiments that address these alternative mechanisms of desensitization.…”