P2Y12 receptor signalling towards PKB proceeds through IGF-I receptor cross-talk and requires activation of Src, Pyk2 and Rap1

Kolen, Kristof Van; Gilany, Kambiz; Moëns, Luc; Esmans, Eddy L.; Slegers, Herman

doi:10.1016/j.cellsig.2005.09.005

Cited by 41 publications

(36 citation statements)

References 70 publications

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“…It has been shown that activation of the P2Y 12 receptor leads to Akt activation through IGF-1 receptor cross-talk in C6 glioma cells. 10 In fact, stimulation of platelets with IGF-1 resulted in Akt phosphorylation. We and others have reported that ADP depends on the G i -coupled P2Y 12 receptor for Akt activation in platelets, and PI3-K activity is necessary for Akt activation in platelets.…”

Section: Discussionmentioning

confidence: 99%

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Insulin-like growth factor-1 regulates platelet activation through PI3-Kα isoform

Kim

Garcia

Jackson

et al. 2007

Blood

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Section: Discussionmentioning

confidence: 99%

“…9 Recent study has shown that P2Y 12 receptor-mediated Akt activation requires IGF-1 receptor in C6 glioma cells. 10 However, the functional role of IGF-1 and its signaling mechanisms in platelet activation are unclear.…”

Section: Introductionmentioning

confidence: 99%

Insulin-like growth factor-1 regulates platelet activation through PI3-Kα isoform

Kim

Garcia

Jackson

et al. 2007

Blood

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“…ERK 1/2 activity was positively correlated with cell proliferation evoked by both P2Y 1 and P2Y 12 receptor agonists, but in serumstarved cells, the effect of ADP on ERK 1/2 was primarily mediated by P2Y 12 receptors [612]. The mechanisms underlying P2Y 12 receptor activation of C6 cells have been studied, and it was concluded that PKB activation proceeds through insulin growth factor I receptor cross-talk and requires activation of Src, Pyk2 and Rap1 [613]. A review discussing P2Y receptor-mediated proliferation and differentiation of glioma cells is available [614].…”

Section: Gliomasmentioning

confidence: 99%

Purinergic signalling and cancer

Burnstock

Virgilio

2013

Purinergic Signalling

262

260

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Receptors for extracellular nucleotides are widely expressed by mammalian cells. They mediate a large array of responses ranging from growth stimulation to apoptosis, from chemotaxis to cell differentiation and from nociception to cytokine release, as well as neurotransmission. Pharma industry is involved in the development and clinical testing of drugs selectively targeting the different P1 nucleoside and P2 nucleotide receptor subtypes. As described in detail in the present review, P2 receptors are expressed by all tumours, in some cases to a very high level. Activation or inhibition of selected P2 receptor subtypes brings about cancer cell death or growth inhibition. The field has been largely neglected by current research in oncology, yet the evidence presented in this review, most of which is based on in vitro studies, although with a limited amount from in vivo experiments and human studies, warrants further efforts to explore the therapeutic potential of purinoceptor targeting in cancer.

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“…In rat C6 glioma cells, activation of the P2Y 12 R by 2MeSATP induced cross-talk with insulinlike growth factor 1 (IGF-I) receptors which proceeded through Gβγ-mediated Ca 2+ influx and phospholipase D2 (PLD2)-dependent activation of the Pyk2/Src pathway, eventually resulting in increased PKB phosphorylation [260]. Insulin-like growth factor 1 (IGF-1) 2MeSADP/P2Y 12 Increased protein kinase B phosphorylation resulting from cross-talk with IGF-1R in C6 glioma cells [260] Together, these studies show that apparent cellular effects of growth factors may be co-initiated by nucleotides or even mediated through nucleotides alone, whereby the molecular mechanisms of receptor interrelation can vary.…”

Section: Nucleotide Activates or Co-activates The Receptor Of Anothermentioning

confidence: 99%

Extracellular ATP and other nucleotides—ubiquitous triggers of intercellular messenger release

Zimmermann

2015

Purinergic Signalling

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Extracellular nucleotides, and ATP in particular, are cellular signal substances involved in the control of numerous (patho)physiological mechanisms. They provoke nucleotide receptor-mediated mechanisms in select target cells. But nucleotides can considerably expand their range of action. They function as primary messengers in intercellular communication by stimulating the release of other extracellular messenger substances. These in turn activate additional cellular mechanisms through their own receptors. While this applies also to other extracellular messengers, its omnipresence in the vertebrate organism is an outstanding feature of nucleotide signaling. Intercellular messenger substances released by nucleotides include neurotransmitters, hormones, growth factors, a considerable variety of other proteins including enzymes, numerous cytokines, lipid mediators, nitric oxide, and reactive oxygen species. Moreover, nucleotides activate or co-activate growth factor receptors. In the case of hormone release, the initially paracrine or autocrine nucleotide-mediated signal spreads through to the entire organism. The examples highlighted in this commentary suggest that acting as ubiquitous triggers of intercellular messenger release is one of the major functional roles of extracellular nucleotides. While initiation of messenger release by nucleotides has been unraveled in many contexts, it may have been overlooked in others. It can be anticipated that additional nucleotide-driven messenger functions will be uncovered with relevance for both understanding physiology and development of therapy.

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P2Y12 receptor signalling towards PKB proceeds through IGF-I receptor cross-talk and requires activation of Src, Pyk2 and Rap1

Cited by 41 publications

References 70 publications

Insulin-like growth factor-1 regulates platelet activation through PI3-Kα isoform

Insulin-like growth factor-1 regulates platelet activation through PI3-Kα isoform

Purinergic signalling and cancer

Extracellular ATP and other nucleotides—ubiquitous triggers of intercellular messenger release

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