Regulation of inositol 1,4,5-trisphosphate-induced Ca2+ release by reversible phosphorylation and dephosphorylation

Abstract

Summary The inositol 1,4,5-trisphosphate (IP3) receptor (IP3R) is a universal intracellular Ca2+-release channel. It is activated after cell stimulation and plays a crucial role in the initiation and propagation of the complex spatio-temporal Ca2+ signals that control cellular processes as different as fertilization, cell division, cell migration, differentiation, metabolism, muscle contraction, secretion, neuronal processing, and ultimately cell death. To achieve these various functions, often in a single cell, exquisite control of the Ca2+ release is needed. This review aims to highlight how protein kinases and protein phosphatases can interact with the IP3R or with associated proteins and so provide a large potential for fine tuning the Ca2+-release activity and for creating efficient Ca2+ signals in subcellular microdomains.

Calmodulin protects against alcohol-induced pancreatic trypsinogen activation elicited via Ca 2+ release through IP 3 receptors

“…IP 3 Rs are the crucial molecules responsible for physiological agonist-elicited intracellular Ca 2+ release and therefore also for normal stimulus-secretion coupling (3,25,32,37,38). Our data now demonstrate the crucial role of types 2 and 3 IP 3 Rs for the pathophysiology of alcohol-related pancreatitis.…”

Regulation of nuclear envelope permeability in cell death and survival

“…To date at least 12 kinases are known to directly phosphorylate the IP3Rs. 54 Treatment with STS, a pan-kinase inhibitor with broad substrate specificity 55 may thus directly interfere with Ca 2+ homeostasis by altering Ca 2+ channel activity. The association of the IP3R inhibitory protein, IRBIT, to IP3Rs is also regulated by phosphorylation.…”

La signalisation calcique dans les lymphocytes T

“…À côté du Ca 2+ et de l'IP3, d'autres signaux intracellulaires peuvent réguler l'activité des RIP3 comme la fixation de nucléotides (ATP) et la phosphorylation par des kinases [13]. De façon intéressante, des kinases susceptibles de moduler l'activité des RIP3, comme la src kinase Fyn, sont activées par la stimulation du TCR et se localisent dans des complexes macromoléculaires contenant le RIP3 de type 1 (RIP3-1) qu'elles phosphorylent.…”

“…De façon intéressante, des kinases susceptibles de moduler l'activité des RIP3, comme la src kinase Fyn, sont activées par la stimulation du TCR et se localisent dans des complexes macromoléculaires contenant le RIP3 de type 1 (RIP3-1) qu'elles phosphorylent. L'aggrégation du RIP3-1 au site d'activation du TCR est due à un mouvement propre du canal vers la plateforme de signalisation associée au TCR [13]. [21,22].…”