CaM kinase II: a protein kinase with extraordinary talents germane to insulin exocytosis.

Easom, Richard A.

doi:10.2337/diabetes.48.4.675

Cited by 119 publications

(106 citation statements)

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“…It is a multigene family comprised of four distinct classes, α, β, γ, and δ, encoded by four separate genes (see Braun and Schulman, 1995;Easom, 1999 for review of CaM kinases expressed in the b cell). Upon activation in high Ca 2+ levels the enzyme that consists of 8-12 subunits undergoes autophosphorylation and increasing degrees of Ca 2+ oscillation results in increasing number of units being autophosphorylated (Easom, 1999). The phosphorylated enzyme has a greater affinity for calmodulin.…”

Section: Calcium/calmodulin Pathwaymentioning

confidence: 99%

Mechanisms of action of glucagon-like peptide 1 in the pancreas

Doyle

Egan

2007

Pharmacology & Therapeutics

583

465

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Glucagon-like peptide-1 is a hormone that is encoded in the proglucagon gene. It is mainly produced in enteroendocrine L cells of the gut and is secreted into the blood stream when food containing fat, protein hydrolysate and/or glucose enters the duodenum. Its particular effects on insulin and glucagon secretion have generated a flurry of research activity over the past twenty years culminating in a naturally occurring GLP-1 receptor agonist, exendin-4, now being used to treat type 2 diabetes. GLP-1 engages a specific G-protein coupled receptor that is present in tissues other than the pancreas (brain, kidney, lung, heart, major blood vessels). The most widely studied cell activated by GLP-1 is the insulin-secreting beta cell where its defining action is augmentation of glucose-induced insulin secretion. Upon GLP-1 receptor activation, adenylyl cyclase is activated and cAMP generated, leading, in turn, to cAMP-dependent activation of second messenger pathways, such as the PKA and Epac pathways. As well as short-term effects of enhancing glucose-induced insulin secretion, continuous GLP-1 receptor activation also increases insulin synthesis, and beta cell proliferation and neogenesis. Although these latter effects cannot be currently monitored in humans, there are substantial improvements in glucose tolerance and increases in both first phase and plateau phase insulin secretory responses in type 2 diabetic patients treated with exendin-4. This review we will focus on the effects resulting from GLP-1 receptor activation in islets of Langerhans

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Section: Calcium/calmodulin Pathwaymentioning

confidence: 99%

Mechanisms of action of glucagon-like peptide 1 in the pancreas

Doyle

Egan

2007

Pharmacology & Therapeutics

583

465

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“…lysophospholipids) and Ca 2ϩ -sensitive kinases and phosphatases (e.g. CaMKII␤ and calcineurin) are also proposed to affect these interactions (9,10,25,32). Mechanisms whereby iPLA 2 ␤ participates in glucose-induced rises in ␤-cell cytosolic [Ca 2ϩ ] and insulin secretion are likely to involve Ca 2ϩ -sensitive regulation of modulatory and effector proteins by phosphorylation-dephosphorylation events (9,10), and iPLA 2 ␤ activity is also affected by local [Ca 2ϩ ] increments that relieve its tonic inhibition by Ca 2ϩ /calmodulin (2,8,25).…”

mentioning

confidence: 99%

Group VIA Phospholipase A2 Forms a Signaling Complex with the Calcium/Calmodulin-dependent Protein Kinase IIβ Expressed in Pancreatic Islet β-Cells

Wang

Ramanadham

Alex

et al. 2005

Journal of Biological Chemistry

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Insulin-secreting pancreatic islet ␤-cells express a Group VIA Ca 2؉ -independent phospholipase A 2 (iPLA 2 ␤) that contains a calmodulin binding site and protein interaction domains. We identified Ca 2؉ /calmodulindependent protein kinase II␤ (CaMKII␤) as a potential iPLA 2 ␤-interacting protein by yeast two-hybrid screening of a cDNA library using iPLA 2 ␤ cDNA as bait. Cloning CaMKII␤ cDNA from a rat islet library revealed that one dominant CaMKII␤ isoform mRNA is expressed by adult islets and is not observed in brain or neonatal islets and that there is high conservation of the isoform expressed by rat and human ␤-cells. Binary two-hybrid assays using DNA encoding this isoform as bait and iPLA 2 ␤ DNA as prey confirmed interaction of the enzymes, as did assays with CaMKII␤ as prey and iPLA 2 ␤ bait. His-tagged CaMKII␤ immobilized on metal affinity matrices bound iPLA 2 ␤, and this did not require exogenous calmodulin and was not prevented by a calmodulin antagonist or the Ca 2؉ chelator EGTA. Activities of both enzymes increased upon their association, and iPLA 2 ␤ reaction products reduced CaMKII␤ activity. Both the iPLA 2 ␤ inhibitor bromoenol lactone and the CaMKII␤ inhibitor KN93 reduced arachidonate release from INS-1 insulinoma cells, and both inhibit insulin secretion. CaMKII␤ and iPLA 2 ␤ can be coimmunoprecipitated from INS-1 cells, and forskolin, which amplifies glucose-induced insulin secretion, increases the abundance of the immunoprecipitatable complex. These findings suggest that iPLA 2 ␤ and CaMKII␤ form a signaling complex in ␤-cells, consistent with reports that both enzymes participate in insulin secretion and that their expression is coinduced upon differentiation of pancreatic progenitor to endocrine progenitor cells.Phospholipases A 2 (PLA 2 ) 1 are a diverse group of enzymes that catalyze hydrolysis of sn-2 fatty acid substituents from glycerophospholipid substrates to yield a free fatty acid and a 2-lysophospholipid (1). The Group VIA PLA 2 designated iPLA 2 ␤ has a molecular mass of 84 -88 kDa and does not require Ca 2ϩ for catalysis (2). Various splice variants of iPLA 2 ␤ are expressed at high levels in testis (3), brain (4), and pancreatic islet ␤-cells (5), among other tissues.Certain nutrients, hormones, neurotransmitters, and pharmacologic agents stimulate insulin secretion from ␤-cells, and the dominant physiologic insulin secretagogue is D-glucose. A series of signals that result from glucose-induced ATP production and alterations of intracellular redox potentials trigger insulin secretion via a rise in cytosolic [Ca 2ϩ ], and Ca 2ϩ /calmodulin-dependent protein kinase II (CaMKII) is an important ␤-cell [Ca 2ϩ ] sensor and mediator of Ca 2ϩ -dependent events in insulin secretion (6 -11). Much evidence (12-22) suggests that iPLA 2 ␤ also participates in insulin secretion, including the facts that the mechanism-based bromoenol lactone (BEL) inhibitor of iPLA 2 ␤ suppresses glucose-induced hydrolysis of arachidonate from islet membrane phospholipids, the rise in ␤-cell cytosolic...

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“…Other studies claim that CaMKII activation is involved in CGE (Markoulaki et al 2003, Sun 2003, Knott et al 2006. As mentioned in the Introduction section, CaMKII, like CaM, is localized at the egg cortex, especially at sites of exocytosis (Shen et al 1998, Easom 1999 and was suggested as a by LCA-biotin (1:100). LCA-biotin was detected by Texas Red Streptavidin (1:1000).…”

Section: Discussionmentioning

confidence: 95%

“…It was hypothesized that CaMKII is required also for CGE and for establishing the block to polyspermy (reviewed by . Although some reports indicate that CaMKII, like CaM, is localized to sites of exocytosis (Shen et al 1998, Easom 1999 and is involved in CGE (Tatone et al 1999, Markoulaki et al 2003); a recent report indicated an abnormal CGE in mouse eggs injected with a constitutively active form of CaMKII (CA-CaMKII; Knott et al 2006).…”

Section: Introductionmentioning

confidence: 99%

Myristoylated alanine-rich C kinase substrate, but not Ca2+/calmodulin-dependent protein kinase II, is the mediator in cortical granules exocytosis

Tsaadon¹,

Kaplan-Kraicer²,

Shalgi³

2008

Reproduction

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Sperm-egg fusion induces cortical granules exocytosis (CGE), a process that ensures the block to polyspermy. CGE can be induced independently by either a rise in intracellular calcium concentration or protein kinase C (PKC) activation. We have previously shown that myristoylated alanine-rich C kinase substrate (MARCKS) cross-links filamentous actin (F-actin) and regulates its reorganization. This activity is reduced either by PKC-induced MARCKS phosphorylation (PKC pathway) or by its direct binding to calmodulin (CaM; CaM pathway), both inducing MARCKS translocation, F-actin reorganization, and CGE. Currently, we examine the involvement of Ca 2C /CaM-dependent protein kinase II (CaMKII) and MARCKS in promoting CGE and show that PKC pathway can compensate for lack of Ca 2C /CaM pathway. Microinjecting eggs with either overexpressed protein or complementary RNA of constitutively active aCaMKII triggered resumption of second meiotic division, but induced CGE of an insignificant magnitude compared with CGE induced by wt aCaMKII. Microinjecting eggs with mutant-unphosphorylatable MARCKS reduced the intensity of 12-O-tetradecanoylphorbol 13-acetate or ionomycin-induced CGE by 50%, indicating that phosphorylation of MARCKS by novel and/or conventional PKCs (n/cPKCs) is a pivotal event associated with CGE. Moreover, we were able to demonstrate cPKCs involvement in ionomycin-induced MARCKS translocation and CGE. These results led us to propose that MARCKS, rather than CaMKII, as a key mediator of CGE. Reproduction (2008) 135 613-624

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CaM kinase II: a protein kinase with extraordinary talents germane to insulin exocytosis.

Cited by 119 publications

References 0 publications

Mechanisms of action of glucagon-like peptide 1 in the pancreas

Mechanisms of action of glucagon-like peptide 1 in the pancreas

Group VIA Phospholipase A2 Forms a Signaling Complex with the Calcium/Calmodulin-dependent Protein Kinase IIβ Expressed in Pancreatic Islet β-Cells

Myristoylated alanine-rich C kinase substrate, but not Ca2+/calmodulin-dependent protein kinase II, is the mediator in cortical granules exocytosis

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