Pertussis toxin activates protein kinase C and a tyrosine protein kinase in the human T cell line Jurkat

Thom, Rebecca E.; Casnellie, John E.

doi:10.1016/0014-5793(89)81188-3

Cited by 30 publications

(24 citation statements)

References 15 publications

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“…These include thrombin (22,30,46), collagen (50), and vasopressin (32) in platelets, fMetLeuPhe in neutrophils (39), muscarinic agonists in hippocampal slices (64), and phytohemagglutinin in Jurkat T cells (69). Disparate findings have been reported regarding the signaling pathways involved in this atypical tyrosine phosphorylation.…”

Section: Discussionmentioning

confidence: 99%

Angiotensin II stimulates protein-tyrosine phosphorylation in a calcium-dependent manner.

Huckle¹,

Prokop²,

Dy³

et al. 1990

Mol. Cell. Biol.

121

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Cellular responses to epidermal growth factor (EGF) are dependent on the tyrosine-specific protein kinase activity of the cell-surface EGF receptor. Previous studies using WB rat liver epithelial cells have detected at least 10 proteins whose phosphotyrosine (P-Tyr) content is increased by EGF. In this study, we have examined alternate modes of activating tyrosine phosphorylation. Treatment of WB cells with hormones linked to Ca2+ mobilization and protein kinase C (PKC) activation, including angiotensin II, [Arg8]vasopressin, or epinephrine, stimulated rapid (<15-s) and transient increases in the P-Tyr content of several proteins (p120/125, p75/78, and p66). These proteins, detected by anti-P-Tyr immunoblotting, were similar in molecular weight to a subset of EGF-sensitive P-Tyr-containing proteins (P-Tyr-proteins all P-Tyr-proteins in response to angiotensin II, thapsigargin, or ionophores, as well as two EGF-stimulated P-Tyr-proteins. The majority of EGF-stimulated P-Tyr-proteins were not affected by BAPTA. These studies indicate that angiotensin II can alter protein-tyrosine phosphorylation in a manner that is secondary to, and apparently dependent on, Ca2+ mobilization. Thus, ligands such as EGF and angiotensin II, which act through distinct types of receptors, may activate secondary pathways involving tyrosine phosphorylation. These results also raise the possibility that certain growth-promoting effects of Ca2+-mobilizing agents such as angiotensin H may be mediated via tyrosine phosphorylation.Reversible phosphorylation of proteins is a major mechanism by which metabolic processes are regulated. Phosphorylation on serine and threonine residues, which together account for >99% of total cellular protein phosphate, are recognized as key elements in the regulation of such diverse pathways as glycogen metabolism, protein biosynthesis, and cell surface receptor signaling (19). Phosphorylation on tyrosine residues, which accounts for <0.5% of proteinbound phosphate (12), has been linked broadly with the control of cell proliferation. Receptors for several growth factors, including epidermal growth factor (EGF) and platelet-derived growth factor, contain ligand-activated, tyrosinespecific protein kinase domains essential for biological activity (76, 78). Similarly, the protein products of several oncogenes (e.g., src and ab) exhibit tyrosine kinase activities essential for oncogenic transformation (36,41).The identities of relevant substrates for tyrosine kinases remain largely obscure because of the technical challenge of monitoring transient tyrosine phosphorylation events against high backgrounds of serine/threonine phosphorylation and because of the complex and temporally protracted nature of mitogenesis. Nevertheless, several potential substrates for tyrosine kinases in intact cells have been identified, using combinations of 32p labeling, electrophoresis, phosphoami-* Corresponding author. no acid analysis, and immunoprecipitation and immunoblotting with antiphosphotyrosine (anti-P-Tyr) antibodies. One gro...

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Section: Discussionmentioning

confidence: 99%

Angiotensin II stimulates protein-tyrosine phosphorylation in a calcium-dependent manner.

Huckle¹,

Prokop²,

Dy³

et al. 1990

Mol. Cell. Biol.

121

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“…It has been shown that, in addition to an effect on G proteinmediated pathways, PTX can have direct, i.e., in the absence of exogenous ligand/receptor stimulation, effects on cellular function. These effects include Ca 2ϩ mobilization (31), cAMP synthesis, diacylglycerol generation (35), tyrosine phosphorylation (36), phosphatase activity (6), and cytoskeletal reorganization (9). In addition, it was demonstrated that PTX changes the activity of several kinases in endothelial cells as follows: p42/p44 MAPK (8), PKC (27), and p38 MAPK (9).…”

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confidence: 98%

Pertussis toxin activatesl-arginine uptake in pulmonary endothelial cells through downregulation of PKC-α activity

Zharikov¹,

Krotova²,

Belayev³

et al. 2004

American Journal of Physiology-Lung Cellular and Molecular Phys

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Pertussis toxin (PTX) induces activation of l-arginine transport in pulmonary artery endothelial cells (PAEC). The effects of PTX on l-arginine transport appeared after 6 h of treatment and reached maximal values after treatment for 12 h. PTX-induced changes in l-arginine transport were not accompanied by changes in expression of cationic amino acid transporter (CAT)-1 protein, the main l-arginine transporter in PAEC. Unlike holotoxin, the beta-oligomer-binding subunit of PTX did not affect l-arginine transport in PAEC, suggesting that Galpha(i) ribosylation is an important step in the activation of l-arginine transport by PTX. An activator of adenylate cyclase, forskolin, and an activator of protein kinase A (PKA), Sp-cAMPS, did not affect l-arginine transport in PAEC. In addition, inhibitors of PKA or adenylate cyclase did not change the activating effect of PTX on l-arginine uptake. Long-term treatment with PTX (18 h) induced a 40% decrease in protein kinase C (PKC)-alpha but did not affect the activities of PKC-epsilon and PKC-zeta in PAEC. An activator of PKC-alpha, phorbol 12-myristate 13-acetate, abrogated the activation of l-arginine transport in PAEC treated with PTX. Incubation of PTX-treated PAEC with phorbol 12-myristate 13-acetate in combination with an inhibitor of PKC-alpha (Go 6976) restored the activating effects of PTX on l-arginine uptake, suggesting PTX-induced activation of l-arginine transport is mediated through downregulation of PKC-alpha. Measurements of nitric oxide (NO) production by PAEC revealed that long-term treatment with PTX induced twofold increases in the amount of NO in PAEC. PTX also increased l-[(3)H]citrulline production from extracellular l-[(3)H]arginine without affecting endothelial NO synthase activity. These results demonstrate that PTX increased NO production through activation of l-arginine transport in PAEC.

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“…Several cell types, including erythrocytes, leukocytes, macrophages, and ciliated cells (33,41,43), display PT receptors on their surface whose precise identity still remains unknown. Although the B oligomer is essentially involved in binding of PT to target cells prior to translocation of the enzymatic S1 subunit, it is by itself also responsible for several biological activities, such as hemagglutination, T-cell mitogenicity, and initiation of signal transduction in target cells (25,30,37).Many reports have established that FHA and PT are necessary for an optimal colonization of the respiratory tract by B. pertussis. Synergy between FHA and PT has also been suspected and has been ascribed to adhesin activities of FHA and PT (40) on macrophages (28, 34) and/or epithelial cells (39,41).…”

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Role of ADP-Ribosyltransferase Activity of Pertussis Toxin in Toxin-Adhesin Redundancy with Filamentous Hemagglutinin duringBordetella pertussisInfection

et al. 2001

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Pertussis toxin (PT) and filamentous hemagglutinin (FHA) are two major virulence factors of Bordetella pertussis. FHA is the main adhesin, whereas PT is a toxin with an A-B structure, in which the A protomer expresses ADP-ribosyltransferase activity and the B moiety is responsible for binding to the target cells. Here, we show redundancy of FHA and PT during infection. Whereas PT-deficient and FHA-deficient mutants colonized the mouse respiratory tract nearly as efficiently as did the isogenic parent strain, a mutant deficient for both factors colonized substantially less well. This was not due to redundant functions of PT and FHA as adhesins, since in vitro studies of epithelial cells and macrophages indicated that FHA, but not PT, acts as an adhesin. An FHA-deficient B. pertussis strain producing enzymatically inactive PT colonized as poorly as did the FHAdeficient, PT-deficient strain, indicating that the ADP-ribosyltransferase activity of PT is required for redundancy with FHA. Only strains producing active PT induced a local transient release of tumor necrosis factor alpha (TNF-␣), suggesting that the pharmacological effects of PT are the basis of the redundancy with FHA, through the release of TNF-␣. This may lead to damage of the pulmonary epithelium, allowing the bacteria to colonize even in the absence of FHA.Many bacterial pathogens produce adhesins and toxins to express their pathogenic potential. Although they are often studied as separate entities, it is possible that in some instances they act in a synergistic or in a redundant way. Redundancy among adhesins has previously been shown (40); however, redundancy between a toxin and an adhesin has not yet been demonstrated. Bordetella pertussis is a human pathogen that causes whooping cough after adherence to and colonization of the respiratory tract. B. pertussis synthesizes a number of virulence factors (16), whose production is under the control of a regulatory locus named bvg. Among them, filamentous hemagglutinin (FHA) and pertussis toxin (PT) have been proven to protect against bacterial infection (4,31,35) and are part of the present acellular vaccines. FHA is a monomeric protein of 220 kDa and has a filamentous structure (20). It is both surface exposed and secreted by B. pertussis. FHA is considered to be the main adhesin of B. pertussis (18) and contains at least three distinct binding sites: a glycosaminoglycan and a carbohydrate binding sites (10, 27) and an arginine-glycine-aspartate (RGD) sequence involved in binding to the CR3 integrin of macrophages (28). PT is an ADP-ribosylating toxin, belonging to the AB 5 family of toxins (17) and is secreted into the extracellular milieu. PT consists of five subunits, named S1 to S5, and can be divided into two functional moieties. The A protomer, corresponding to the S1 subunit, expresses the ADP-ribosyltransferase activity. The B oligomer, composed of subunits S2 to S5, mediates binding of PT to its target cell receptors through the carbohydrate recognition domains of the S2 and S3 subunits (43)....

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Pertussis toxin activates protein kinase C and a tyrosine protein kinase in the human T cell line Jurkat

Cited by 30 publications

References 15 publications

Angiotensin II stimulates protein-tyrosine phosphorylation in a calcium-dependent manner.

Angiotensin II stimulates protein-tyrosine phosphorylation in a calcium-dependent manner.

Pertussis toxin activatesl-arginine uptake in pulmonary endothelial cells through downregulation of PKC-α activity

Role of ADP-Ribosyltransferase Activity of Pertussis Toxin in Toxin-Adhesin Redundancy with Filamentous Hemagglutinin duringBordetella pertussisInfection

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