Na<sup>+</sup>/H<sup>+</sup> exchange is not necessary for protein kinase C‐mediated effects in platelets

Krishnamurthi, Sushila; Patel, Yatin; Morgan, Winston A.; Wheeler‐Jones, Caroline P.D.; Kakkar, Vijay V.

doi:10.1016/0014-5793(89)80908-1

Cited by 8 publications

(7 citation statements)

References 29 publications

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“…The possible physiological significance of the above in vitro results on PLAZ and sphingosine is uncertain. Yet, in this context, it might be of interest to note that thrombin-induced arachidonate release in human platelets was strongly reduced in the presence of sphingosine in spite of the elevated levels of intracellular Ca2+ (Krishnamurthi et al, 1989). Sphingosine also blocked arachidonic acid release and PLAZ activity in neutrophils (McIntyreet al, 1987) and smooth musclecells (Chakraborti et al, 1991).…”

Section: Biochemistrymentioning

confidence: 96%

Effects of sphingosine on peripheral membrane interactions: Comparison of adriamycin, cytochrome c, and phospholipase A2

Mustonen¹,

Lehtonen²,

Kõiv³

et al. 1993

Biochemistry

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As revealed by resonance energy transfer utilizing pyrene-labeled phosphatidylcholine donor, the mainly electrostatically controlled binding of adriamycin (Adr) and cytochrome c (cyt c) to mixed egg yolk phosphatidic acid/phosphatidylcholine (eggPA/eggPC, 15:85 molar ratio) liposomes was reversed upon the inclusion of increasing contents of sphingosine. At a [sphingosine]/[eggPA] molar ratio of approximately 2:1, the degree of fluorescence quenching by cyt c and Adr was approximately the same as when using liposomes lacking eggPA. Similarly, the increase in the surface pressure of sphingosine/eggPA monolayers on an air/water interface due to the membrane penetration of either cyt c or Adr was progressively reduced by increasing the content of sphingosine in the monolayers. The above critical [sphingosine]/[acidic phospholipid] stoichiometry yielding dissociation of the positively charged ligands Adr or cyt c from membrane acidic phospholipids was shifted from 2:1 to 1:1 upon substituting egg phosphatidylglycerol (eggPG) for eggPA. Accordingly, charge neutralization of the acidic phospholipids by sphingosine could be involved. One eggPA (having maximally two negative charges) appears to require two molecules of sphingosine whereas the maximally singly charged eggPG is neutralized by one sphingosine. For comparison we also studied the effects of sphingosine on the phospholipase A2 catalyzed hydrolysis of the pyrene-labeled acidic alkylacyl phospholipid analog 1-octacosanyl-2-[6-(pyren-1-yl)]hexanoyl-sn-glycero-3- phosphatidylmethanol (C28-O-PHPM) and the corresponding phosphatidylcholine (C28-O-PHPC). In the presence of low Ca2+ concentrations (approximately 50 nM) limiting the rate of the enzymatic reaction, sphingosine gradually inhibited the hydrolysis of phosphatidylcholine, and at 1:6 sphingosine/C28-O-PHPC a nearly complete lack of hydrolysis was evident.(ABSTRACT TRUNCATED AT 250 WORDS)

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Section: Biochemistrymentioning

confidence: 96%

Effects of sphingosine on peripheral membrane interactions: Comparison of adriamycin, cytochrome c, and phospholipase A2

Mustonen¹,

Lehtonen²,

Kõiv³

et al. 1993

Biochemistry

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“…The activation of PKC has been demonstrated to perturb signalling through thrombin and TXA # . Pretreating platelets with PKC-activating phorbol esters results in the inhibition of PTX-resistant increases in intracellular calcium (presumably from increased inositol phosphate production) in response to either thrombin or TXA # [154,155]. One group correlated this PKC-dependent inhibition with the concomitant phosphorylation of G i α2, thus implicating this G-protein in thrombin and TXA # signalling [155].…”

Section: Plateletsmentioning

confidence: 98%

Signalling functions and biochemical properties of pertussis toxin-resistant G-proteins

Fields

Casey

1997

Biochemical Journal

255

192

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Pertussis toxin (PTX) has been widely used as a reagent to characterize the involvement of heterotrimeric G-proteins in signalling. This toxin catalyses the ADP-ribosylation of specific G-protein alpha subunits of the Gi family, and this modification prevents the occurrence of the receptor-G-protein interaction. This review focuses on the biochemical properties and signalling of those G-proteins historically classified as 'PTX-resistant' due to the inability of the toxin to influence signalling through them. These G-proteins include members of the Gq and G12 families and one Gi family member, i.e. Gz. Signalling pathways controlled by these G-proteins are well characterized only for Gq family members, which activate specific isoforms of phospholipase C, resulting in increases in intracellular calcium and activation of protein kinase C (PKC), among other responses. While members of the G12 family have been implicated in processes that regulate cell growth, and Gz has been shown to inhibit adenylate cyclase, the specific downstream targets to these G-proteins in vivo have not been clearly established. Since two of these proteins, G12 alpha and Gz alpha, are excellent substrates for PKC, there is the potential for cross-talk between their signalling and Gq-dependent processes leading to activation of PKC. In tissues that express these G-proteins, a number of guanine-nucleotide-dependent, PTX-resistant, signalling pathways have been defined for which the G-protein involved has not been identified. This review summarizes these pathways and discusses the evidence both for the participation of specific PTX-resistant G-proteins in them and for the regulation of these processes by PKC.

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“…In platelets, excitatory agonists promote the generation of Ins(1,4,5)P $ and diacylglycerol, which respectively result in an elevation of intracellular Ca# + and activation of PKC, the major receptor for tumour-promoting phorbol esters [14]. There is now substantial evidence to support the involvement of PKC in both the initiation and termination of cellular signals elicited by receptor-operating platelet agonists [15], and at least three isoforms of PKC have been identified in human platelets [16]. Although there is some evidence that the different isoforms of PKC are differentially regulated during platelet activation [17,18], there is no information available about the potential physiological role of endogenous PKC inhibitors in these cells.…”

Section: Introductionmentioning

confidence: 99%

Identification of 14-3-3 proteins in human platelets: effects of synthetic peptides on protein kinase C activation

Wheeler‐Jones

Learmonth²,

Hennenberg³

et al. 1996

Biochemical Journal

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The 14-3-3 proteins inhibit protein kinase C (PKC) activity in vitro and contain conserved sequences that resemble the pseudosubstrate domain of PKC and the C-terminus of the annexins. In the present study we have identified the isoforms of 14-3-3 in human platelets and used synthetic peptides derived from the regions with similarity to PKC and annexins to examine the potential role of 14-3-3 in regulating platelet activity. Immunoblotting studies with isoform-specific antisera raised against the acetylated peptides corresponding to the N-termini of 14-3-3 showed that these cells express high levels of the beta, gamma and zeta 14-3-3 isoforms. In addition, low levels of the epsilon and eta 14-3-3 isoforms were detected. In washed, saponin-permeabilized platelets incubated with [gamma-32P]ATP, thrombin- and phorbol 12-myristate 13-acetate (PMA)-induced phosphorylation of several proteins (66, 45, and 20kDa) was inhibited by preincubation with AS peptide (KNVVGARRSSWRVISSIEQK) based on the pseudosubstrate-like region of the 14-3-3 family. A control peptide of similar size had no effect on PKC-mediated phosphorylation. PMA caused a rapid translocation of PKC activity from the cytosol to the particulate fraction of saponin-permeabilized platelets that was unaffected by either the AS peptide or a peptide derived from the annexin-like 14-3-3 domain (MKGDYYRYLAEVATGDD). These results suggest that isoforms of the 14-3-3 family may play an important physiological role as inhibitors of PKC activity in human platelets but are unlikely to be involved in controlling association of PKC with the membrane.

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Na⁺/H⁺ exchange is not necessary for protein kinase C‐mediated effects in platelets

Cited by 8 publications

References 29 publications

Effects of sphingosine on peripheral membrane interactions: Comparison of adriamycin, cytochrome c, and phospholipase A2

Effects of sphingosine on peripheral membrane interactions: Comparison of adriamycin, cytochrome c, and phospholipase A2

Signalling functions and biochemical properties of pertussis toxin-resistant G-proteins

Identification of 14-3-3 proteins in human platelets: effects of synthetic peptides on protein kinase C activation

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Na+/H+ exchange is not necessary for protein kinase C‐mediated effects in platelets

Cited by 8 publications

References 29 publications

Effects of sphingosine on peripheral membrane interactions: Comparison of adriamycin, cytochrome c, and phospholipase A2

Effects of sphingosine on peripheral membrane interactions: Comparison of adriamycin, cytochrome c, and phospholipase A2

Signalling functions and biochemical properties of pertussis toxin-resistant G-proteins

Identification of 14-3-3 proteins in human platelets: effects of synthetic peptides on protein kinase C activation

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Na⁺/H⁺ exchange is not necessary for protein kinase C‐mediated effects in platelets