Differential regulation of SHC proteins by nerve growth factor in sensory neurons and PC12 cells

Ganju, Pam; O’Bryan, John P.; Der, Channing J.; Winter, Janet; James, Iain F.

doi:10.1046/j.1460-9568.1998.00209.x

Cited by 58 publications

(38 citation statements)

References 79 publications

(139 reference statements)

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“…This is further supported by the observation that RAI and oncogenic isoforms of RET (RET/ PTC1 or RET/MEN2A) are coexpressed in a series of cell lines derived from thyroid malignancies in which RET is involved, PTCs and MTCs. It is interesting to note that RAI expression has been reported to be restricted to the nervous system in post-mitotic neurons (Ganju et al, 1998;Nakamura et al, 1998;Tanabe et al, 1998;Conti et al, 2001). Despite this, we found expression of RAI in human cell lines derived from human thyroid tumors.…”

Section: Discussionmentioning

confidence: 52%

RAI(ShcC/N-Shc)-dependent recruitment of GAB1 to RET oncoproteins potentiates PI3-K signalling in thyroid tumors

et al. 2005

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RAI, also named ShcC/N-Shc, one of the members of the Shc proteins family, is a substrate of the RET receptor tyrosine kinase. Here, we show that RAI forms a protein complex with both RET/MEN2A and RET/PTC oncoproteins. By coimmunoprecipitation, we found that RAI associates with the Grb2-associated binder1 (GAB1) adapter. This association is constitutive, but, in the presence of RET oncoproteins, both RAI and GAB1 are tyrosine-phosphorylated, and the stoichiometry of this interaction remarkably increases. Consequently, the p85 regulatory subunit of phosphatidylinositol-3 kinase (PI-3K) is recruited to the complex, and its downstream effector Akt is activated. We show that human thyroid cancer cell lines derived from papillary or medullary thyroid carcinoma (PTC or MTC) carrying, respectively, RET/PTC and RET/MEN2A oncoproteins express RAI proteins. We also show that human PTC samples express higher levels of RAI, when compared to normal thyroid tissue. In thyroid cells expressing RET/PTC1, ectopic expression of RAI protects cells from apoptosis; on the other hand, the silencing of endogenous RAI by small inhibitory duplex RNAs in a PTC cell line that expresses endogenous RET/PTC1, increases the rate of spontaneous apoptosis. These data suggest that RAI is a critical substrate for RET oncoproteins in thyroid carcinomas.

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Section: Discussionmentioning

confidence: 52%

RAI(ShcC/N-Shc)-dependent recruitment of GAB1 to RET oncoproteins potentiates PI3-K signalling in thyroid tumors

et al. 2005

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“…The mechanism of NGF sensitizing the nociceptor of the primary afferent neurons was recently elucidated. 50 In addition to this, NGF influences properties of the primary afferent neurons and increases the maximum amount of electric discharge that the axon can conduct. 51 Based on these reports, NGF itself may act as an algesic substance.…”

Section: Discussionmentioning

confidence: 99%

The autotomy relief effect of a silicone tube covering the proximal nerve stump

et al. 2006

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A technique of covering the proximal nerve stump (PNS) has been reported as a preventative method or treatment for neuroma. However, its detailed pain relief mechanism remains unknown. We created a silicone tube model in which the PNS of the rat sciatic nerve was introduced into the tube, whereas the controls had no tube. The score of autotomy observed in the tube group was lower than that in the control group at 3 days to 2 weeks after surgery, which suggested that the silicone tube had pain-like behavior inhibitory action. To elucidate the mechanism of autotomy inhibition, immunohistochemistry and Toluidine blue staining were performed in the PNS. The increase in S-100-immunoreactivity (IR) including Schwann cells was inhibited at 1 week after surgery in the tube group, and the increase in the number of macrophages shown by ED-1-IR at 1, 2, and 4 weeks after surgery was similarly inhibited. Toluidine blue staining showed that the increase in the number of mast cells was inhibited at 1, 2, and 4 weeks after surgery and in the number of lymphocytes at 1 and 2 weeks after surgery in the tube group. Therefore, blocking of the infiltration of inflammatory cells into the PNS by the silicone tube was thought to be the mechanism of autotomy inhibition. To further explore details of this mechanism, the expression of nerve growth factor (NGF), production of which is induced by inflammatory cells and of the NGF receptor TrkA was examined in the PNS and the dorsal root ganglion using immunohistochemistry and a ribonuclease protection assay. In the PNS, the increase in NGF-IR was inhibited at 1, 2, and 4 weeks after surgery in the tube group, suggesting that this could be one of the pain-like behavior inhibitory effects. ß

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“…This result seemed to indicate that plastic changes in VR1 expression might not play a critical role in the expression of inflammationinduced thermal hyperalgesia. In the development of inflammation, VR1 itself may act as the heat-transducing molecule that is sensitized by inflammatory mediators (Burgess et al 1989;Chuang et al 2001) or NGF (Ganju et al 1998;McMahon and Bennett 1999), which is perhaps the main pathway mediating the important role of VR1 in inflammation-induced hyperalgesia. However, considering that carrageenan or CFA treatment increased peripheral capsaicin receptor expression (Carlton and Coggeshall 2001;Tohda et al 2001) and that much of the newly synthesized VR1 in DRG neurons would be transported toward the peripheral terminals (Guo et al 1999), an increase in VR1 expression cannot be completely excluded at present.…”

Section: Discussionmentioning

confidence: 99%

State‐dependent phosphorylation of ε‐isozyme of protein kinase C in adult rat dorsal root ganglia after inflammation and nerve injury

Zhou

Zhao

2003

Journal of Neurochemistry

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The e-isozyme of protein kinase C (PKCe) and the vanilloid receptor 1 (VR1) are both expressed in dorsal root ganglion (DRG) neurons and are reported to be predominantly and specifically involved in nociceptive function. Using phosphospecific antibody against the C-terminal hydrophobic site Ser729 of PKCe as a marker of enzyme activation, the statedependent activation of PKCe, as well as the expression of VR1 in rat DRG neurons, was evaluated in different experimental pain models in vivo. Quantitative analysis showed that phosphorylation of PKCe in DRG neurons was significantly up-regulated after carrageen-and Complete Freund's Adjuvant-induced inflammation, while it was markedly downregulated after chronic constriction injury. A double-labeling study showed that phosphorylation of PKCe was expressed predominantly in VR1 immunoreactivity positive small diameter DRG neurons mediating the nociceptive information from peripheral tissue to spinal cord. The VR1 protein expression showed no significant changes after either inflammation or chronic constriction injury. These data indicate that functional activation of PKCe has a close relationship with the production of inflammatory hyperalgesia and the sensitization of the nociceptors. Inflammatory mediator-induced activation of PKCe and subsequent sensitization of VR1 to noxious stimuli by PKCe may be involved in nociceptor sensitization.

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Differential regulation of SHC proteins by nerve growth factor in sensory neurons and PC12 cells

Cited by 58 publications

References 79 publications

RAI(ShcC/N-Shc)-dependent recruitment of GAB1 to RET oncoproteins potentiates PI3-K signalling in thyroid tumors

RAI(ShcC/N-Shc)-dependent recruitment of GAB1 to RET oncoproteins potentiates PI3-K signalling in thyroid tumors

The autotomy relief effect of a silicone tube covering the proximal nerve stump

State‐dependent phosphorylation of ε‐isozyme of protein kinase C in adult rat dorsal root ganglia after inflammation and nerve injury

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