Thrombin Primes Responsiveness of Selective Chemoattractant Receptors at a Site Distal to G Protein Activation

Ali, Hydar; Tomhave, Eric; Richardson, Ricardo M.; Haribabu, Bodduluri; Snyderman, Ralph

doi:10.1074/jbc.271.6.3200

Cited by 32 publications

(21 citation statements)

References 47 publications

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“…4D). In rat basophilic leukemia RBL-2H3 cells, a similar potentiating ("priming") effect of thrombin on the chemoattractant-induced release of InsP 3 was observed which also lasted several minutes (38). These cross-talk events between two different receptor-effector systems may thus require signaling components distal to receptors and their associated G proteins.…”

Section: Discussionmentioning

confidence: 84%

“…Suppression-In addition to activating an effector system directly, receptor-mediated stimulation of hematopoietic cells may also result in potentiating the action of a second ligand that is administered simultaneously with, or subsequently to, the primary agonist (31,37,38). Thus, the stimulation of HEL cells with UTP (100 M) prior to challenging with PGE 1 substantially enhanced the mobilization of intracellular Ca 2ϩ by the second agonist (Fig.…”

Section: Utp Generates a Potentiating Effect On Pge 1 -Induced Changementioning

confidence: 99%

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The P2U Purinoceptor Obligatorily Engages the Heterotrimeric G Protein G16 to Mobilize Intracellular Ca2+ in Human Erythroleukemia Cells

Baltensperger

Porzig

1997

Journal of Biological Chemistry

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To assess the role of G 16 , a trimeric G protein exclusively expressed in hematopoietic cells, G ␣16 antisense RNA was stably expressed in human erythroleukemia (HEL) cells. Western blot analysis showed that in transfected cell lines, the expression of endogenous G ␣16 protein was suppressed, but the expression of G ␣q/11 , G ␣i2 , and G ␣i3 remained unaffected. Suppression of G ␣16 in transfected HEL cells did not interfere with transient elevations of intracellular free Ca 2؉ concentrations induced by prostaglandin E 1 (PGE 1 ), platelet-activating factor, or thrombin. In parental HEL cells, UTP and ATP mobilized Ca 2؉ from intracellular stores with half-maximum effective concentrations of 3.6 ؎ 0.7 and 4.7 ؎ 1.6 M, respectively, apparently by stimulating P 2U purinoceptors. By contrast, Ca 2؉ mobilization by UTP or ATP was completely abrogated in G ␣16 -suppressed cells, indicating specific coupling of G 16 to P 2U purinoceptors. Pertussis toxin inhibited the effect of UTP in parental HEL cells by 57.6 ؎ 4.9%. These data indicate that signaling by the P 2U purinoceptor obligatorily requires G 16 but may be modulated further by activation of G i . Priming of HEL cells with UTP or ATP prior to stimulation with PGE 1 markedly enhanced the PGE 1 -induced intracellular Ca 2؉ release. This indirect, potentiating effect of UTP and ATP was not impaired in G ␣16 -suppressed cells but was inhibited by pertussis toxin, indicating that functional P 2U purinoceptors are present on these cells and that the potentiating effect primarily depends on G i . The data demonstrate (i) that G ␣16 antisense RNA selectively inhibits endogenous G ␣16 protein expression in HEL cells; (ii) that stimulation of endogenous P 2U (P2Y 2 ) purinoceptors leads to the mobilization of intracellular Ca 2؉ by a mechanism that strictly depends on G ␣16 ; and (iii) that P 2U purinoceptors in HEL cells can communicate with two distinct signaling pathways diverging at the G protein level.

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Section: Discussionmentioning

confidence: 84%

Section: Utp Generates a Potentiating Effect On Pge 1 -Induced Changementioning

confidence: 99%

The P2U Purinoceptor Obligatorily Engages the Heterotrimeric G Protein G16 to Mobilize Intracellular Ca2+ in Human Erythroleukemia Cells

Baltensperger

Porzig

1997

Journal of Biological Chemistry

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“…Accordingly, some cytokine enhancement of thrombin receptor expression and thrombin induction of cytokine receptors have been published. 41,42 In addition, in vascular endothelial cells thrombin potentiates TNF-␣-induced nuclear factor-B activity that is known to participate in the induction of IL-8, MCP-1, and IL-6 gene transcription. 43 Therefore, thrombin and cytokines may affect each others receptor expression and/or signaling pathways.…”

Section: Discussionmentioning

confidence: 99%

Thrombin Regulates Chemokine Induction during Human Retinal Pigment Epithelial Cell/Monocyte Interaction

Yoshida

Elner

Bian

et al. 2001

The American Journal of Pathology

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“…Mast cells have thrombin receptors that couple to G q , a pertussis toxin-insensitive G-protein ␣-subunit and A 3 adenosine receptors that couple to a pertussis toxin-sensitive ␣-subunit G i . The stimulation of these receptors in RBL-2H3 cells results in a transient increase in intracellular Ca 2ϩ (39,40). Here we observed that stimulation of the cells with either thrombin or an adenosine analog induced the rapid tyrosine phosphorylation of Pyk2.…”

Section: Pyk2 Is Tyrosine-phosphorylated and Activated After Fc⑀rimentioning

confidence: 99%

“…Stimulation of thrombin and adenosine G-protein-coupled receptors in RBL-2H3 cells results in transient mobilization of intracellular calcium (39,40). Thrombin stimulation is mediated by a pertussis toxin-insensitive G-protein, whereas adenosine is inhibited by this toxin, suggesting that it is probably mediated by G i (39,41). Stimulation with thrombin of both the RBL-2H3 and the Syk-negative TB1A2 cells induced the rapid tyrosine phosphorylation of Pyk2 (Fig.…”

Section: Pyk2 Is Tyrosine-phosphorylated and Activated After Fc⑀rimentioning

confidence: 99%

Activation of Protein-tyrosine Kinase Pyk2 Is Downstream of Syk in FcεRI Signaling

Okazaki

Zhang

Hamawy

et al. 1997

Journal of Biological Chemistry

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Aggregation of the Fc⑀RI, a member of the immune receptor family, induces the activation of proteintyrosine kinases and results in tyrosine phosphorylation of proteins that are involved in downstream signaling pathways. Here we report that Pyk2, another member of the focal adhesion kinase family, was present in the RBL-2H3 mast cell line and was rapidly tyrosinephosphorylated and activated after Fc⑀RI aggregation. Tyrosine phosphorylation of Pyk2 was also induced by the calcium ionophore A23187, by phorbol myristate acetate, or by stimulation of G-protein-coupled receptors. Adherence of cells to fibronectin dramatically enhanced the induced tyrosine phosphorylation of Pyk2. Although Src family kinases are activated by Fc⑀RI stimulation and tyrosine-phosphorylate the receptor subunits, the activation and tyrosine phosphorylation of Pyk2 were downstream of Syk. In contrast, tyrosine phosphorylation of Pyk2 by stimulation of G-protein-coupled receptors was independent of Syk. Therefore, the Fc⑀RI-induced tyrosine phosphorylation of Pyk2 is downstream of Syk and may play a role in cell secretion.The aggregation of the Fc⑀RI 1 on basophils or mast cells initiates a cascade of biochemical events that results in degranulation and the release of inflammatory mediators (1, 2). Tyrosine phosphorylation of proteins plays a critical role in this signal transduction pathway (3-8). Among the signal transduction molecules that are tyrosine-phosphorylated are the ␤ and ␥ subunits of the receptor, Lyn, Syk, phospholipase C-␥1 and -␥2, Vav, Btk, and the focal adhesion kinase FAK (9 -15). One of the earliest events after aggregation of Fc⑀RI is the activation of protein-tyrosine kinases, probably Lyn or another Src family kinase, that results in the tyrosine phosphorylation of the ␤ and ␥ subunits of the receptor (9, 16). The proteintyrosine kinase Syk is then recruited by the tyrosine-phosphorylated receptor and is critical for the downstream activation signals (11,(17)(18)(19). For example, Fc⑀RI aggregation in a Sykdeficient mast cell line does not mobilize Ca 2ϩ from intracellular and extracellular sources and fails to propagate downstream signaling events (20).Previously we observed that Fc⑀RI aggregation results in the tyrosine phosphorylation of ϳ115-kDa proteins in the rat basophilic leukemia RBL-2H3 mast cell line (21,22). Two of these proteins were identified as FAK and the cell surface adhesion molecule CD31 (15,23). Recently Pyk2 was identified as another member of the FAK family of protein-tyrosine kinases (24 -26). Pyk2 (also called RAFTK for related adhesion focal tyrosine kinase, CAK␤ for cell adhesion kinase ␤, CADTK and FAK2) is a cytoplasmic protein-tyrosine kinase that, like FAK, lacks a transmembrane region, myristoylation sites, and Src homology 2 and 3 domains. Both FAK and Pyk2 have a central kinase region flanked by large N-terminal and C-terminal domains. Pyk2 is expressed in neuronal cells, CD34ϩ bone marrow cells, primary bone marrow megakaryocytes, platelets, and T and B cells (24,26,27).

show abstract

Thrombin Primes Responsiveness of Selective Chemoattractant Receptors at a Site Distal to G Protein Activation

Cited by 32 publications

References 47 publications

The P2U Purinoceptor Obligatorily Engages the Heterotrimeric G Protein G16 to Mobilize Intracellular Ca2+ in Human Erythroleukemia Cells

The P2U Purinoceptor Obligatorily Engages the Heterotrimeric G Protein G16 to Mobilize Intracellular Ca2+ in Human Erythroleukemia Cells

Thrombin Regulates Chemokine Induction during Human Retinal Pigment Epithelial Cell/Monocyte Interaction

Activation of Protein-tyrosine Kinase Pyk2 Is Downstream of Syk in FcεRI Signaling

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