INT89845
From wiki-pain
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Sentences Mentioned In
Key: | Protein | Mutation | Event | Anatomy | Negation | Speculation | Pain term | Disease term |
Over the past decade, a large body of evidence has accumulated showing that a main function of Src is to upregulate the activity of N-methyl-D-aspartate (NMDA) receptors and other ion channels. | |||||||||||||||
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The NMDA receptor currents must be further enhanced during the high frequency stimulation by the calcium-dependent activation of Pyk2 and Src kinases in order to induce LTP [5]. | |||||||||||||||
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Finally, even though SRC represents an acute form of renal involvement, vascular pathology may be observed in SSc patients in the absence of SRC. | |||||||||||||||
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Our findings (Battaglia et al., 2003, and present work) support the idea of an activation by ephrinB2 of postsynaptic EphB receptors in neurons of the dorsal horn, since we showed that EphB1 receptors are present in dorsal horn neurons, where they are found in close association with NMDA receptors, and intrathecal administration of ephrinB2-Fc induces an increase in phosphorylated Src kinase associated with the EphB receptor itself. | |||||||||||||||
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We therefore formulated the hypothesis that EphB receptors are involved in synaptic plasticity in vivo in the spinal cord (underlying chronic pain states) via a mechanism involving Src activation and NR2B phosphorylation. | |||||||||||||||
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The mechanism apparently involved Src family kinases, since the level of phospho-Src bound to EphB receptors in the dorsal horns of the spinal cord was increased. | |||||||||||||||
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Interestingly, they also found that, in the absence of SRC, a significant increase in arterial fibrointimal thickness was observed in dcSSc patients, and to a lesser extent in lcSSc patients, compared to controls. | |||||||||||||||
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In the present study, we investigated whether Src activity contributed to this sorting pattern and to functional desensitization of DORs. | |||||||||||||||
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Such vascular changes may be due to the presence of mild ongoing renal vascular injury below the threshold which triggers SRC.
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The identification of Abl as a downstream target in hippocampal neurons coupled with the requirement of Src to fully activate Abl after PDGF receptor activation may help reconcile the apparent contradiction in the requirement of Src for an inhibition of NMDA receptor currents by PDGF receptor activation and the direct potentiation of NMDA receptors by Src [14]. | |||||||||||||||
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Activation of Src kinase via the phosphorylation of tyrosine 416 is associated with a potentiation of NMDA receptor currents and an increase in long-term potentiation [40-42]. | |||||||||||||||
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The identification of Abl as a downstream target in hippocampal neurons coupled with the requirement of Src to fully activate Abl after PDGF receptor activation may help reconcile the apparent contradiction in the requirement of Src for an inhibition of NMDA receptor currents by PDGF receptor activation and the direct potentiation of NMDA receptors by Src [14]. | |||||||||||||||
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Interestingly, PDGF-BB treatment increased the phosphorylation of Src at both tyrosine 416 (tyrosine phosphorylation here potentiates Src activity) and 527 (tyrosine phosphorylation inhibits Src activity) [39]. | |||||||||||||||
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Indeed, EphB2 activation of Src by phosphorylation in cultured hippocampal and cortical neurons could induce NR2A phosphorylation (Grunwald et al., 2001). | |||||||||||||||
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Interestingly, Takasu et al. (2002) showed that in primary cortical neurons in culture EphB activation by ephrinB2-Fc (immunoglobulin Fc fusion protein of ephrinB2) induced Src-dependent NR2B phosphorylation and furthermore we showed that intrathecal injection of ephrinB2-Fc induces Src phosphorylation in the spinal cord of adult rats (Battaglia et al., 2003). | |||||||||||||||
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We did not reprobe for amounts of total Src/Fyn/Yes as total levels of those proteins bound to NR2B are directly affected by phosphorylation, i.e. phosphorylation promotes the association of the proteins to NR2B (Yu et al., 1997); the ratio of phospho-Src/total Src could thus potentially remain constant despite a significant increase in the total amount of activated phospho-Src bound to NR2B. | |||||||||||||||
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We have found that in the absence of MOR activation, the brain specific Galphaz subunit binds to and stabilizes Src in its inactive form. | |||||||||||||||
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Internalization and Src activity regulate the time course of ERK activation by delta opioid receptor ligands. | |||||||||||||||
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enhances NMDA receptor-mediated Ca2+ responses via activating tyrosine protein kinase Src [94], which is known to enhance NMDA receptor activity in dorsal horn neurons [52, 95]. | |||||||||||||||
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Previously, we showed that selective delta-opioid agonists were able to induce the rapid tyrosine phosphorylation of delta-opioid receptors (delta-ORs) through Src. | |||||||||||||||
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General Comments
This test has worked.