Protein kinase C controls Fcγ receptor‐mediated endocytosis in human neutrophils

Moraru, Ion I.; Laky, Mariana; Stãnescu, T; Buzilă, L; Popescu, L. M.

doi:10.1016/0014-5793(90)81337-n

Cited by 20 publications

(4 citation statements)

References 22 publications

(29 reference statements)

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“…Therefore, involvement of PKC in cellular events is obtained by sequential administration of an active-site directed inhibitor of PKC ( e.g. Ro32-0432) and a phorbol ester [26], [27]. (Ro32-0432 will inhibit a Ser/Thr kinase whose active site architecture is similar to that of PKC even if the enzyme lacks a C1-domain).…”

Section: Resultsmentioning

confidence: 99%

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Diacylglycerol-Stimulated Endocytosis of Transferrin in Trypanosomatids Is Dependent on Tyrosine Kinase Activity

Subramanya

Mensa-Wilmot

2010

PLoS ONE

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Small molecule regulation of cell function is an understudied area of trypanosomatid biology. In Trypanosoma brucei diacylglycerol (DAG) stimulates endocytosis of transferrin (Tf). However, it is not known whether other trypanosomatidae respond similarly to the lipid. Further, the biochemical pathways involved in DAG signaling to the endocytic system in T. brucei are unknown, as the parasite genome does not encode canonical DAG receptors (e.g. C1-domains). We established that DAG stimulates endocytosis of Tf in Leishmania major, and we evaluated possible effector enzymes in the pathway with multiple approaches. First, a heterologously expressed glycosylphosphatidylinositol phospholipase C (GPI-PLC) activated endocytosis of Tf 300% in L. major. Second, exogenous phorbol ester and DAGs promoted Tf endocytosis in L. major. In search of possible effectors of DAG signaling, we discovered a novel C1-like domain (i.e. C1_5) in trypanosomatids, and we identified protein Tyr kinases (PTKs) linked with C1_5 domains in T. brucei, T. cruzi, and L. major. Consequently, we hypothesized that trypanosome PTKs might be effector enzymes for DAG signaling. General uptake of Tf was reduced by inhibitors of either Ser/Thr or Tyr kinases. However, DAG-stimulated endocytosis of Tf was blocked only by an inhibitor of PTKs, in both T. brucei and L. major. We conclude that (i) DAG activates Tf endocytosis in L. major, and that (ii) PTKs are effectors of DAG-stimulated endocytosis of Tf in trypanosomatids. DAG-stimulated endocytosis of Tf may be a T. brucei adaptation to compete effectively with host cells for vertebrate Tf in blood, since DAG does not enhance endocytosis of Tf in human cells.

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Section: Resultsmentioning

confidence: 99%

“…6). Second, in vertebrates a majority of DAG signaling pathways depend on Ser/Thr kinases (PKCs) [26], [51], [52]. In contrast, DAG-stimulated endocytosis of Tf in T. brucei and L. major depends on protein Tyr kinase (Fig.…”

Section: Discussionmentioning

confidence: 99%

Diacylglycerol-Stimulated Endocytosis of Transferrin in Trypanosomatids Is Dependent on Tyrosine Kinase Activity

Subramanya

Mensa-Wilmot

2010

PLoS ONE

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“…For example, administration of low concentrations of palmitoylcarnitine (≤10 μM) altered PKC activity in a variety of cell types. In addition, this treatment also partially blocked the ability of some tumour-promoting agents to inhibit gap-junction intercellular communication in a rat liver epithelial cell line; 83 reduced Fcγ receptor-mediated endocytosis in human neutrophils; 84 and triggered terminal differentiation and reduced proliferation of leukaemia cells 85 and neuroblastoma cells. 86 …”

Section: A Working Model Of Lcac Functionsmentioning

confidence: 95%

Acylcarnitines—old actors auditioning for new roles in metabolic physiology

2015

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Perturbations in metabolic pathways can cause substantial increases in plasma and tissue concentrations of long-chain acylcarnitines (LCACs). For example, the levels of LCACs and other acylcarnitines rise in the blood and muscle during exercise, as changes in tissue pools of acylcoenzyme A reflect accelerated fuel flux that is incompletely coupled to mitochondrial energy demand and capacity of the tricarboxylic acid cycle. This natural ebb and flow of acylcarnitine generation and accumulation contrasts with that of inherited fatty acid oxidation disorders (FAODs), cardiac ischaemia or type 2 diabetes mellitus. These conditions are characterized by very high (FAODs, ischaemia) or modestly increased (type 2 diabetes mellitus) tissue and blood levels of LCACs. Although specific plasma LCAC concentrations and chain-lengths are widely used as diagnostic markers of FAODs, research into the potential effects of excessive LCAC accumulation or the roles of acylcarnitines as physiological modulators of cell metabolism is lacking. Nevertheless, a growing body of evidence has highlighted possible effects of LCACs on disparate aspects of pathophysiology, such as cardiac ischaemia outcomes, insulin sensitivity and inflammation. This Review, therefore, aims to provide a theoretical framework for the potential consequences of tissue build-up of LCACs among persons with metabolic disorders.

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“…Furthermore, while sphingosine is a major endogenous lipid in neutrophils, its cellular levels are negatively regulated during neutrophil activation (Wilson et al, 1988). Exogenous sphingosine was subsequently used as a tool to establish the role of PKC as an activator of Fcγ receptors (FcγR)-mediated endocytosis (Moraru et al, 1990). …”

Section: Sphingolipids In Neutrophil Regulationmentioning

confidence: 99%

Sphingolipids in neutrophil function and inflammatory responses: Mechanisms and implications for intestinal immunity and inflammation in ulcerative colitis

Espaillat

Kew

Obeid

2017

Advances in Biological Regulation

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Bioactive sphingolipids are regulators of immune cell function and play critical roles in inflammatory conditions including ulcerative colitis. As one of the major forms of inflammatory bowel disease, ulcerative colitis pathophysiology is characterized by an aberrant intestinal inflammatory response that persists causing chronic inflammation and tissue injury. Innate immune cells play an integral role in normal intestinal homeostasis but their dysregulation is thought to contribute to the pathogenesis of ulcerative colitis. In particular, neutrophils are key effector cells and are first line defenders against invading pathogens. While the activity of neutrophils in the intestinal mucosa is required for homeostasis, regulatory mechanisms are equally important to prevent unnecessary activation. In ulcerative colitis, unregulated neutrophil inflammatory mechanisms promote tissue injury and loss of homeostasis. Aberrant neutrophil function represents an early checkpoint in the detrimental cycle of chronic intestinal inflammation; thus, dissecting the mechanisms by which these cells are regulated both before and during disease is essential for understanding the pathogenesis of ulcerative colitis. We present an analysis of the role of sphingolipids in the regulation of neutrophil function and the implication of this relationship in ulcerative colitis.

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Protein kinase C controls Fcγ receptor‐mediated endocytosis in human neutrophils

Cited by 20 publications

References 22 publications

Diacylglycerol-Stimulated Endocytosis of Transferrin in Trypanosomatids Is Dependent on Tyrosine Kinase Activity

Diacylglycerol-Stimulated Endocytosis of Transferrin in Trypanosomatids Is Dependent on Tyrosine Kinase Activity

Acylcarnitines—old actors auditioning for new roles in metabolic physiology

Sphingolipids in neutrophil function and inflammatory responses: Mechanisms and implications for intestinal immunity and inflammation in ulcerative colitis

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