Phospholipase C-δ1 Is Activated by Capacitative Calcium Entry That Follows Phospholipase C-β Activation upon Bradykinin Stimulation

Kim, Yong Hyun; Park, Tae‐Ju; Lee, Young Han; Baek, Kwang Jin; Suh, Pann‐Ghill; Ryu, Sung Ho; Kim, Kyong‐Tai

doi:10.1074/jbc.274.37.26127

Cited by 116 publications

(89 citation statements)

References 44 publications

(36 reference statements)

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“…2A). However, cotransfection of PLC-⑀ with G␤ 1 ␥ 2 produced marked increases in [ 3 H]inositol phosphate accumulation to levels similar to those observed with G␣ 12 or G␣ 13 (Fig. 2A).…”

Section: Fig 1 Domain Organization Of Plc Isozymes and Secondary Stmentioning

confidence: 73%

“…2A). Cotransfection of maximally effective concentrations of G␤ 1 ␥ 2 and G␣ 12 (or G␣ 13 ) with PLC-⑀ produced no greater activity than with cotransfection of PLC-⑀ with each subunit alone (data not shown). Similarly, co-expression of G␤ 1 ␥ 2 together with GTPase-deficient, constitutively active mutants of G␣ 12 (Q229L) or G␣ 13 (Q226L) resulted in activity similar to that observed with the GTPasedeficient mutant alone (Fig.…”

Section: Fig 1 Domain Organization Of Plc Isozymes and Secondary Stmentioning

confidence: 99%

“…PLC-␥ isozymes are activated by protein phosphorylation following from activation of tyrosine kinase receptors or from receptors linked to tyrosine kinases (10 -12). Although there is evidence for Ca 2ϩ -and transglutaminase II-promoted regulation of PLC-␦ (13,14), the importance of hormonal regulation of this PLC isozyme remains unclear (15).…”

Section: Plcmentioning

confidence: 99%

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Activation of Phospholipase C-ε by Heterotrimeric G Protein βγ-Subunits

Wing

Houston

Kelley

et al. 2001

Journal of Biological Chemistry

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PLC-⑀ was identified recently as a phosphoinositidehydrolyzing phospholipase C (PLC) containing catalytic domains (X, Y, and C2) common to all PLC isozymes as well as unique CDC25-and Ras-associating domains. Novel regulation of this PLC isozyme by the Ras oncoprotein and ␣-subunits (G␣ 12 ) of heterotrimeric G proteins was illustrated. Sequence analyses of PLC-⑀ revealed previously unrecognized PH and EF-hand domains in the amino terminus. The known interaction of G␤␥ subunits with the PH domains of other proteins led us to examine the capacity of G␤␥ to activate PLC-⑀.

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Section: Fig 1 Domain Organization Of Plc Isozymes and Secondary Stmentioning

confidence: 73%

Section: Fig 1 Domain Organization Of Plc Isozymes and Secondary Stmentioning

confidence: 99%

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Activation of Phospholipase C-ε by Heterotrimeric G Protein βγ-Subunits

Wing

Houston

Kelley

et al. 2001

Journal of Biological Chemistry

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“…Although we have not formally assessed the PLC␦ family members in this context, we consider their involvement highly unlikely. As is the case in other cell types (14,15), PLC␦ is known to be activated in ␤-cells as a direct consequence of a rise in intracellular Ca 2ϩ (36). Although this is sufficient to promote PtdInsP 2 hydrolysis in pancreatic islets (37), we have previously shown this was not the case for PtdIns breakdown (10).…”

Section: Discussionmentioning

confidence: 85%

“…The recently discovered protein kinase C⑀ is a component of ras signaling pathways (11)(12)(13). PLC␦ is the most sensitive of the PLC family to Ca 2ϩ , and a rise in intracellular Ca 2ϩ is thought to underly its activation in vivo (14,15). The PLC␥ family members (PLC␥ 1 and 2) are classically activated downstream of receptor tyrosine kinases, but they also couple to muscarinic and other GPCRs in a manner secondary to stimulation of cytosolic tyrosine kinases (3,4,16,17).…”

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confidence: 99%

Phospholipase C-γ Mediates the Hydrolysis of Phosphatidylinositol, but Not of Phosphatidylinositol 4,5-Bisphoshate, in Carbamylcholine-stimulated Islets of Langerhans

Mitchell

Kelly

Blewitt

et al. 2001

Journal of Biological Chemistry

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In pancreatic islets the activation of phospholipase C (PLC) by the muscarinic receptor agonist carbamyolcholine (carbachol) results in the hydrolysis of both phosphatidylinositol 4,5-bisphosphate (PtdInsP 2 ) and phosphatidylinositol (PtdIns). Here we tested the hypothesis that PtdIns hydrolysis is mediated by PLC␥1, which is known to be regulated by activation of tyrosine kinases and PtdIns 3-kinase. PtdIns breakdown was more sensitive than that of PtdInsP 2 to the tyrosine kinase inhibitor, genistein. Conversely, the tyrosine phosphatase inhibitor, vanadate, alone promoted PtdIns hydrolysis and acted non-additively with carbachol. Vanadate did not stimulate PtdInsP 2 breakdown. Carbachol also stimulated a rapid (maximal at 1-2 min) tyrosine phosphorylation of several islet proteins, although not of PLC␥1 itself. Two structurally unrelated inhibitors of PtdIns 3-kinase, wortmannin and LY294002, more effectively attenuated the hyrolysis of PtdIns compared with PtdInsP 2 . Adenovirally mediated overexpression of PLC␥1 significantly increased carbachol-stimulated PtdIns hydrolysis without affecting that of PtdInsP 2 . Conversely overexpression of PLC␤1 up-regulated the PtdInsP 2 , but not PtdIns, response. These results indicate that the hydrolysis of PtdIns and PtdInsP 2 are independently regulated in pancreatic islets and that PLC␥1 selectively mediates the breakdown of PtdIns. The activation mechanism of PLC␥ involves tyrosine phosphorylation (but not of PLC␥ directly) and PtdIns 3-kinase. Our findings point to a novel bifurcation of signaling pathways downstream of muscarinic receptors and suggest that hydrolysis of PtdIns and PtdInsP 2 might serve different physiological ends.Many receptor tyrosine kinases and GPCRs 1 couple to PLC that catalyzes the cleavage of PtdInsP 2 and resultant generation of the two second messengers Ins(1,4,5)P 3 , which mobilizes Ca 2ϩ from intracellular stores, and DAG, which activates protein kinase C (1-4). These pathways are well described in the regulation of insulin secretion following occupation of m3 and m1 muscarinic receptors on the surface of pancreatic ␤Ϫcells (5-8). However we have shown that in addition to the classical pathway of PtdInsP 2 hydrolysis, exposure of pancreatic islets to the muscarinic receptor agonist carbachol also promotes the hydrolysis of PtdIns (9, 10). The latter predominates quantitatively over, and is a precursor of, PtdInsP 2 . Although hydrolysis of either phosphoinositide species results in generation of DAG, only PtdInsP 2 gives rise to a Ca 2ϩ signal via Ins(1,4,5)P 3 production. Therefore the two hydrolytic events may have different functional consequences. The inositol phosphate, corresponding to Ins(1,4,5)P 3 , that is derived from PtdIns, is Ins(1)P 1 . This has no biological function but can be used to quantify PtdIns hydrolysis, at least under the conditions verified in our previous studies (9).The PLC family is comprised of four major groups (PLCs ␤, ␥, ␦, and ⑀). Members of the PLC␤ family are activated by Gproteins in response to o...

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Phosphorylation of Phospholipase C‐δ₁ Regulates its Enzymatic Activity

Fujii

Kim

et al. 2009

J of Cellular Biochemistry

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Phosphorylation of phospholipase C-delta(1) (PLC-delta(1)) in vitro and in vivo was investigated. Of the serine/threonine kinases tested, protein kinase C (PKC) phosphorylated the serine residue(s) of bacterially expressed PLC-delta(1) most potently. It was also demonstrated that PLC-delta(1) directly bound PKC-alpha via its pleckstrin homology (PH) domain. Using deletion mutants of PLC-delta(1) and synthetic peptides, Ser35 in the PH domain was defined as the PKC mediated in vitro phosphorylation site of PLC-delta(1). In vitro phosphorylation of PLC-delta(1) by PKC stimulated [(3)H]PtdIns(4,5)P(2) hydrolyzing activity and [(3)H]Ins(1,4,5)P(3)-binding of the PLC-delta(1). On the other hand, endogenous PLC-delta(1) was constitutively phosphorylated and phosphoamino acid analysis revealed that major phosphorylation sites were threonine residues in quiescent cells. The phosphorylation level and the species of phosphoamino acid were not changed by various stimuli such as PMA, EGF, NGF, and forskolin. Using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry, we determined that Thr209 of PLC-delta(1) is one of the constitutively phosphorylated sites in quiescent cells. The PLC activity was potentiated when constitutively phosphorylated PLC-delta(1) was dephosphorylated by endogenous phosphatase(s) in vitro. Additionally, coexpression with PKC-alpha reduced serine phosphorylation of PLC-delta(1) detected by an anti-phosphoserine antibody and PLC-delta(1)-dependent basal production of inositol phosphates in NIH-3T3 cells, suggesting PKC-alpha activates phosphatase or inactivates another kinase involved in PLC-delta(1) serine phosphorylation to modulate the PLC-delta(1) activity in vivo. Taken together, these results suggest that PLC-delta(1) has multiple phosphorylation sites and phosphorylation status of PLC-delta(1) regulates its activity positively or negatively depends on the phosphorylation sites.

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Phospholipase C-δ1 Is Activated by Capacitative Calcium Entry That Follows Phospholipase C-β Activation upon Bradykinin Stimulation

Cited by 116 publications

References 44 publications

Activation of Phospholipase C-ε by Heterotrimeric G Protein βγ-Subunits

Activation of Phospholipase C-ε by Heterotrimeric G Protein βγ-Subunits

Phospholipase C-γ Mediates the Hydrolysis of Phosphatidylinositol, but Not of Phosphatidylinositol 4,5-Bisphoshate, in Carbamylcholine-stimulated Islets of Langerhans

Phosphorylation of Phospholipase C‐δ₁ Regulates its Enzymatic Activity

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Phospholipase C-δ1 Is Activated by Capacitative Calcium Entry That Follows Phospholipase C-β Activation upon Bradykinin Stimulation

Cited by 116 publications

References 44 publications

Activation of Phospholipase C-ε by Heterotrimeric G Protein βγ-Subunits

Activation of Phospholipase C-ε by Heterotrimeric G Protein βγ-Subunits

Phospholipase C-γ Mediates the Hydrolysis of Phosphatidylinositol, but Not of Phosphatidylinositol 4,5-Bisphoshate, in Carbamylcholine-stimulated Islets of Langerhans

Phosphorylation of Phospholipase C‐δ1 Regulates its Enzymatic Activity

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Phosphorylation of Phospholipase C‐δ₁ Regulates its Enzymatic Activity