Evidence for a role of myosin phosphorylation in the initiation of the platelet shape change response.

Daniel, James L.; Molish, Ilean R.; Rigmaiden, Marilyn; Stewart, Gwendolyn J.

doi:10.1016/s0021-9258(17)42774-8

Cited by 200 publications

(19 citation statements)

References 19 publications

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“…However, we have found that in certain experimental conditions these agonists can stimulate the platelets to change shape and to secrete the contents of amine storage granules even when [Ca2+1] remains at, or close to, basal levels (< 300 nM), and well below the levels needed to cause shape-change (400 nM) and secretion (> 1 ,UM) when calcium ionophore is used to stimulate the cells (Hallam et al, 1984a;Rink et al, 1982a;. We therefore wondered whether the same might be true for myosin phosphorylation, since this phosphorylation has been proposed to be an important element in the cytoplasmic rearrangements involved in shape-change and secretion in platelets (Daniel et al, 1984a). We tested this idea by measuring myosin phosphorylation after quin2-loaded platelets had been stimulated with PAF and thrombin in a medium containing no added calcium and 1 mM-EGTA.…”

Section: Measurement Of External Ca2+mentioning

confidence: 99%

“…We do not know at present precisely what is the functional role of myosin light chain phosphorylation in platelets. Recent evidence shows a strong correlation between ADP-evoked shapechange and the extent of phosphorylation of myosin chains (Daniel et al, 1984a). It seems possible that phosphorylation plays a major role in the internal reorganization of organelles, sometimes referred to as internal contraction, that accompanies a full shape-change response (Gerrard et al, 1979).…”

Section: Experimental Conditionsmentioning

confidence: 99%

“…Myosin light-chain kinase is found in platelets and is activated in vitro by calcium and calmodulin (Scholey et al, 1980), and in intact platelets, calcium ionophore stimulates the phosphorylation of myosin light chains, Mr 20000 (Kaibuchi et al, 1983). It has therefore been supposed that physiological stimuli promote myosin phosphorylation by elevating cytoplasmic free calcium, [Ca2+], (Daniel et al, 1984a;Adelstein & Eisenberg, 1980). We have examined myosin phosphorylation in human platelets loaded with quin2, the intracellular fluorescent Ca2+ indicator, to examine, for the first time in intact cells, the relation between cytoplasmic free calcium and myosin phosphorylation.…”

Section: Introductionmentioning

confidence: 99%

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Relationship between cytoplasmic free calcium and myosin light chain phosphorylation in intact platelets

Hallam¹,

Daniel²,

Kendrick‐Jones³

et al. 1985

Biochemical Journal

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Human platelets were prepared and loaded with the fluorescent Ca2+ indicator quin2. The relation between cytoplasmic free calcium concentration, [Ca2+]i, and the extent of the phosphorylation of myosin light chains of Mr 20 000 could then be examined. When the calcium ionophore ionomycin is used to stimulate platelets, little phosphorylation is seen until [Ca2+]i exceeds 400 nM; half-maximal response occurs at 600 nM with a full response at about 1 microM-[Ca2+]i. Under optimal conditions, physiological stimuli such as platelet-activating factor and thrombin can increase [Ca2+]i to sufficiently high levels [Rink, Smith & Tsien (1982) FEBS Lett. 148, 21-26; Hallam, Sanchez & Rink (1984) Biochem. J. 218, 819-827] that Ca2+ ions could be the trigger for the myosin phosphorylation evoked by these agonists. However, in this paper we show that, in the absence of external calcium, platelet-activating factor and thrombin can stimulate myosin phosphorylation while [Ca2+]i remains at levels which are well below those needed when the calcium ionophore is the stimulus. This observation suggests that myosin light chain phosphorylation may be controlled by an additional pathway.

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Section: Measurement Of External Ca2+mentioning

confidence: 99%

Section: Experimental Conditionsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Relationship between cytoplasmic free calcium and myosin light chain phosphorylation in intact platelets

Hallam¹,

Daniel²,

Kendrick‐Jones³

et al. 1985

Biochemical Journal

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“…Long MLCK is a central regulator in immune-mediated barrier loss [ 40 - 42 ]. It also affects cell division and proliferation [ 43 ] and cell shape [ 44 , 45 ].…”

Section: Discussionmentioning

confidence: 99%

Myosin light chain kinase is a potential target for hypopharyngeal cancer treatment

Cao

Zhu

Zhang

et al. 2020

Biomedicine & Pharmacotherapy

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Hypopharyngeal cancer is squamous cell carcinoma (SCC) with the worst prognosis among the head and neck cancers. Overall, the 5-year survival rate remains poor although diagnostic imaging, radiation, chemotherapy, and surgical techniques have been improved. The mortality of patients with hypopharyngeal cancer is partly due to an increased likelihood of developing a second primary malignancy and metastasis. In this study, we found that MLCK expression, compared to healthy tissue, was up-regulated in hypopharyngeal tumor tissue. Of particular interest, a low 5-year survival rate was positively correlated with MLCK expression. We hypothesized that MLCK might be a target for hypopharyngeal cancer prognosis and treatment. In order to explore the function of MLCK in the development of cancer, we knockdown MLCK in hypopharyngeal cancer FaDu cells. The results showed that MLCK knockdown reduced the migration and invasion of FaDu cells. 4-amino-2-trifluoromethylphenyl retinate (ATPR) is the derivative of all-trans retinoic acid (ATRA), which was able to reduce both MLCK expression and activity in FaDu cells. ATPR induced FaDu cells apoptosis in a dose-dependent manner and also inhibited cell growth both in vivo and in vitro . Further experiments showed that overexpression of MLCK reduced ATPR induced-migration inhibition while increase of ATPR induced apoptosis, which suggested that MLCK was involved in ATPR’s anti-cancer function. In conclusion, MLCK is a novel prognostic marker and therapeutic target for hypopharyngeal cancer. By targeting MLCK, ATPR exhibits its potential application in the treatment of this type of cancer.

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“…A very important protein involved in cytoskeleton reorganization is MLC. The phosphorylation of the 20 kDa MLC is one of the primary steps in the activation of actomyosin contractile events, which leads to reorganization of the cytoskeleton structure, shape change and secretion . In smooth muscle, MLC is found to be phosphorylated on residues thr18 and/or ser19 by Rho kinase (ROCK) which can be activated by the small GTP binding protein RhoA and/or by the Ca 2+ /CaM‐dependent MLC kinase (MLCK) .…”

Section: Discussionmentioning

confidence: 99%

Activation of CaMKKβ/AMPKα pathway by 2‐AG in human platelets

Signorello

Leoncini

2017

J of Cellular Biochemistry

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The objective of this study was to determine whether AMPK is activated by 2-arachidonoylglycerol (2-AG) and participates to the cytoskeleton control in human platelets. We found that 2-AG stimulates the AMPKα activation through a Ca 2 + /Calmodulin-dependent pathway as the specific inhibition of the CaMKKβ by STO-609 inhibits the AMPKα phosphorylation/activation. Moreover, the CaMKKβ/ AMPKα pathway activated by 2-AG is involved in the phosphorylation of cofilin, vasodilator stimulated phosphoprotein (VASP), and myosin light chain (MLCs). These proteins participate to actin cytoskeletal remodelling during aggregation. We found that the phosphorylation/activation inhibition of these proteins is associated with a significant reduction in actin polymerization, aggregation, ATP, and α-granule secretion. Finally, AMPKα activation, Cofilin, VASP, and MLCs phosphorylation are significantly reduced by SR141716, the specific inhibitor of type 1 cannabinoid (CB1) receptor, suggesting that the CB1 receptor is involved in the 2-AG effect. In conclusion, we have shown that the CaMKKβ/AMPKα pathway is activated by 2-AG in human platelets and controls the phosphorylation of key proteins involved in actin polymerization and aggregation.

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Evidence for a role of myosin phosphorylation in the initiation of the platelet shape change response.

Cited by 200 publications

References 19 publications

Relationship between cytoplasmic free calcium and myosin light chain phosphorylation in intact platelets

Relationship between cytoplasmic free calcium and myosin light chain phosphorylation in intact platelets

Myosin light chain kinase is a potential target for hypopharyngeal cancer treatment

Activation of CaMKKβ/AMPKα pathway by 2‐AG in human platelets

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