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The calcitonin receptor stimulates Shc tyrosine phosphorylation and Erk1/2 activation. Involvement of Gi, protein kinase C, and calcium

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The calcitonin receptor stimulates Shc tyrosine phosphorylation and Erk1/2 activation. Involvement of Gi, protein kinase C, and calcium. / Chen, Y; Shyu, J F; Santhanagopal, A; Inoue, D; David, J P; Dixon, S J; Horne, W C; Baron, R.

In: J BIOL CHEM, Vol. 273, No. 31, 31.07.1998, p. 19809-16.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Chen, Y, Shyu, JF, Santhanagopal, A, Inoue, D, David, JP, Dixon, SJ, Horne, WC & Baron, R 1998, 'The calcitonin receptor stimulates Shc tyrosine phosphorylation and Erk1/2 activation. Involvement of Gi, protein kinase C, and calcium', J BIOL CHEM, vol. 273, no. 31, pp. 19809-16.

APA

Chen, Y., Shyu, J. F., Santhanagopal, A., Inoue, D., David, J. P., Dixon, S. J., Horne, W. C., & Baron, R. (1998). The calcitonin receptor stimulates Shc tyrosine phosphorylation and Erk1/2 activation. Involvement of Gi, protein kinase C, and calcium. J BIOL CHEM, 273(31), 19809-16.

Vancouver

Chen Y, Shyu JF, Santhanagopal A, Inoue D, David JP, Dixon SJ et al. The calcitonin receptor stimulates Shc tyrosine phosphorylation and Erk1/2 activation. Involvement of Gi, protein kinase C, and calcium. J BIOL CHEM. 1998 Jul 31;273(31):19809-16.

Bibtex

@article{ffd54e41950d484a9458993dee512fc8,
title = "The calcitonin receptor stimulates Shc tyrosine phosphorylation and Erk1/2 activation. Involvement of Gi, protein kinase C, and calcium",
abstract = "While it is well established that adenylyl cyclase and phospholipase C-beta are two proximal signal effectors for the calcitonin receptor, the more distal signaling pathways are less well characterized. G protein-coupled receptors can activate Erk1/2 by Gs-, Gi-, or Gq-dependent signaling pathways, depending on the specific receptor and cell type examined. Since the calcitonin receptor can couple to all three of these G proteins, the ability of calcitonin to activate Erk1/2 was investigated. Calcitonin induced time- and concentration-dependent increases in Shc tyrosine phosphorylation, Shc-Grb2 association and Erk1/2 phosphorylation and activation in a HEK 293 cell line that stably expresses the rabbit calcitonin receptor C1a isoform. Pertussis toxin, which inactivates Gi, and calphostin C, a protein kinase C inhibitor, each partially inhibited calcitonin-induced Shc tyrosine phosphorylation, Shc-Grb2 association, and Erk1/2 phosphorylation. In contrast, neither forskolin nor H89, a protein kinase A inhibitor, had a significant effect on basal or calcitonin-stimulated Erk1/2 phosphorylation. Our results suggest that the calcitonin receptor induces Shc phosphorylation and Erk1/2 activation in HEK293 cells by parallel Gi- and PKC-dependent mechanisms. The calcitonin-induced elevation of cytosolic free Ca2+ was required for Erk1/2 phosphorylation, since preventing any change in cytosolic free Ca2+ by chelating both cytosolic and extracellular Ca2+ abolished the response. However, the change in Ca2+ that is induced by calcitonin is not sufficient to account for the calcitonin-induced Erk1/2 phosphorylation, since treatment with 100 nM ionomycin or 10 microM thapsigargin, each of which induced elevations of Ca2+ comparable to those induced by calcitonin, induced significantly less Erk1/2 phosphorylation than that induced by calcitonin. Erk1/2 may have important roles as downstream effectors mediating cellular responses to calcitonin stimulation.",
keywords = "Adaptor Proteins, Signal Transducing, Adaptor Proteins, Vesicular Transport, Adenylate Cyclase Toxin, Animals, Calcitonin, Calcium, Calcium-Calmodulin-Dependent Protein Kinases, Cell Line, Colforsin, Enzyme Activation, Enzyme Inhibitors, GRB2 Adaptor Protein, GTP-Binding Proteins, Ionomycin, Pertussis Toxin, Phosphorylation, Phosphotyrosine, Protein Kinase C, Proteins, Rabbits, Receptors, Calcitonin, Shc Signaling Adaptor Proteins, Tyrosine, Virulence Factors, Bordetella",
author = "Y Chen and Shyu, {J F} and A Santhanagopal and D Inoue and David, {J P} and Dixon, {S J} and Horne, {W C} and R Baron",
year = "1998",
month = jul,
day = "31",
language = "English",
volume = "273",
pages = "19809--16",
journal = "J BIOL CHEM",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "31",

}

RIS

TY - JOUR

T1 - The calcitonin receptor stimulates Shc tyrosine phosphorylation and Erk1/2 activation. Involvement of Gi, protein kinase C, and calcium

AU - Chen, Y

AU - Shyu, J F

AU - Santhanagopal, A

AU - Inoue, D

AU - David, J P

AU - Dixon, S J

AU - Horne, W C

AU - Baron, R

PY - 1998/7/31

Y1 - 1998/7/31

N2 - While it is well established that adenylyl cyclase and phospholipase C-beta are two proximal signal effectors for the calcitonin receptor, the more distal signaling pathways are less well characterized. G protein-coupled receptors can activate Erk1/2 by Gs-, Gi-, or Gq-dependent signaling pathways, depending on the specific receptor and cell type examined. Since the calcitonin receptor can couple to all three of these G proteins, the ability of calcitonin to activate Erk1/2 was investigated. Calcitonin induced time- and concentration-dependent increases in Shc tyrosine phosphorylation, Shc-Grb2 association and Erk1/2 phosphorylation and activation in a HEK 293 cell line that stably expresses the rabbit calcitonin receptor C1a isoform. Pertussis toxin, which inactivates Gi, and calphostin C, a protein kinase C inhibitor, each partially inhibited calcitonin-induced Shc tyrosine phosphorylation, Shc-Grb2 association, and Erk1/2 phosphorylation. In contrast, neither forskolin nor H89, a protein kinase A inhibitor, had a significant effect on basal or calcitonin-stimulated Erk1/2 phosphorylation. Our results suggest that the calcitonin receptor induces Shc phosphorylation and Erk1/2 activation in HEK293 cells by parallel Gi- and PKC-dependent mechanisms. The calcitonin-induced elevation of cytosolic free Ca2+ was required for Erk1/2 phosphorylation, since preventing any change in cytosolic free Ca2+ by chelating both cytosolic and extracellular Ca2+ abolished the response. However, the change in Ca2+ that is induced by calcitonin is not sufficient to account for the calcitonin-induced Erk1/2 phosphorylation, since treatment with 100 nM ionomycin or 10 microM thapsigargin, each of which induced elevations of Ca2+ comparable to those induced by calcitonin, induced significantly less Erk1/2 phosphorylation than that induced by calcitonin. Erk1/2 may have important roles as downstream effectors mediating cellular responses to calcitonin stimulation.

AB - While it is well established that adenylyl cyclase and phospholipase C-beta are two proximal signal effectors for the calcitonin receptor, the more distal signaling pathways are less well characterized. G protein-coupled receptors can activate Erk1/2 by Gs-, Gi-, or Gq-dependent signaling pathways, depending on the specific receptor and cell type examined. Since the calcitonin receptor can couple to all three of these G proteins, the ability of calcitonin to activate Erk1/2 was investigated. Calcitonin induced time- and concentration-dependent increases in Shc tyrosine phosphorylation, Shc-Grb2 association and Erk1/2 phosphorylation and activation in a HEK 293 cell line that stably expresses the rabbit calcitonin receptor C1a isoform. Pertussis toxin, which inactivates Gi, and calphostin C, a protein kinase C inhibitor, each partially inhibited calcitonin-induced Shc tyrosine phosphorylation, Shc-Grb2 association, and Erk1/2 phosphorylation. In contrast, neither forskolin nor H89, a protein kinase A inhibitor, had a significant effect on basal or calcitonin-stimulated Erk1/2 phosphorylation. Our results suggest that the calcitonin receptor induces Shc phosphorylation and Erk1/2 activation in HEK293 cells by parallel Gi- and PKC-dependent mechanisms. The calcitonin-induced elevation of cytosolic free Ca2+ was required for Erk1/2 phosphorylation, since preventing any change in cytosolic free Ca2+ by chelating both cytosolic and extracellular Ca2+ abolished the response. However, the change in Ca2+ that is induced by calcitonin is not sufficient to account for the calcitonin-induced Erk1/2 phosphorylation, since treatment with 100 nM ionomycin or 10 microM thapsigargin, each of which induced elevations of Ca2+ comparable to those induced by calcitonin, induced significantly less Erk1/2 phosphorylation than that induced by calcitonin. Erk1/2 may have important roles as downstream effectors mediating cellular responses to calcitonin stimulation.

KW - Adaptor Proteins, Signal Transducing

KW - Adaptor Proteins, Vesicular Transport

KW - Adenylate Cyclase Toxin

KW - Animals

KW - Calcitonin

KW - Calcium

KW - Calcium-Calmodulin-Dependent Protein Kinases

KW - Cell Line

KW - Colforsin

KW - Enzyme Activation

KW - Enzyme Inhibitors

KW - GRB2 Adaptor Protein

KW - GTP-Binding Proteins

KW - Ionomycin

KW - Pertussis Toxin

KW - Phosphorylation

KW - Phosphotyrosine

KW - Protein Kinase C

KW - Proteins

KW - Rabbits

KW - Receptors, Calcitonin

KW - Shc Signaling Adaptor Proteins

KW - Tyrosine

KW - Virulence Factors, Bordetella

M3 - SCORING: Journal article

C2 - 9677414

VL - 273

SP - 19809

EP - 19816

JO - J BIOL CHEM

JF - J BIOL CHEM

SN - 0021-9258

IS - 31

ER -