Evidence for the involvement of two pathways in activation of extracellular signal-regulated kinase (Erk) and cell proliferation by Gi and Gq protein-coupled receptors in osteoblast-like cells

J. Caverzasio, G. Palmer, Atsushi Suzuki, J. P. Bonjour

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

The mechanisms by which Gi and Gq protein-coupled receptors mediate mitogenic signaling in osteoblast-like cells are unknown and were investigated in MC3T3-E1 cells using specific receptor agonists such as lysophosphatidic acid (LPA) and prostaglandin F(2α) (PGF(2α)). In contrast to their implication in epidermal growth factor (EGF) receptor tyrosine kinase signaling, the adaptor protein Shc, the Grb2/Sos complex, and the small G protein Ras were not involved in the activation of Erk induced by either LPA or PGF(2α) in MC3T3-E1 cells, suggesting that activation of Erk by Gi and Gq protein-coupled receptors is Ras independent in these cells. Using specific kinase inhibitors and kinetic analyses, we provide evidence for two distinct components in the activation of Erk by Gi and Gq protein-coupled receptors in MC3T3-E1 cells including an Src-like kinase-dependent pathway and a protein kinase C (PKC)-dependent mechanism. Functional analyses suggested that these two components are required for optimal DNA synthesis in response to LPA and PGF(2α). These results suggest the implication of two pathways in the stimulation of Erk and cell replication by growth factors acting through Gi and Gq protein-coupled receptors in bone-forming cells.

Original languageEnglish
Pages (from-to)1697-1706
Number of pages10
JournalJournal of Bone and Mineral Research
Volume15
Issue number9
DOIs
Publication statusPublished - 01-01-2000

Fingerprint

Gq-G11 GTP-Binding Protein alpha Subunits
Extracellular Signal-Regulated MAP Kinases
Osteoblasts
Cell Proliferation
Prostaglandins F
Shc Signaling Adaptor Proteins
Monomeric GTP-Binding Proteins
src-Family Kinases
Epidermal Growth Factor Receptor
Protein-Tyrosine Kinases
Protein Kinase C
Intercellular Signaling Peptides and Proteins
Phosphotransferases
Bone and Bones
DNA

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine

Cite this

@article{e64e718bbc7a4372b418db3fc377efef,
title = "Evidence for the involvement of two pathways in activation of extracellular signal-regulated kinase (Erk) and cell proliferation by Gi and Gq protein-coupled receptors in osteoblast-like cells",
abstract = "The mechanisms by which Gi and Gq protein-coupled receptors mediate mitogenic signaling in osteoblast-like cells are unknown and were investigated in MC3T3-E1 cells using specific receptor agonists such as lysophosphatidic acid (LPA) and prostaglandin F(2α) (PGF(2α)). In contrast to their implication in epidermal growth factor (EGF) receptor tyrosine kinase signaling, the adaptor protein Shc, the Grb2/Sos complex, and the small G protein Ras were not involved in the activation of Erk induced by either LPA or PGF(2α) in MC3T3-E1 cells, suggesting that activation of Erk by Gi and Gq protein-coupled receptors is Ras independent in these cells. Using specific kinase inhibitors and kinetic analyses, we provide evidence for two distinct components in the activation of Erk by Gi and Gq protein-coupled receptors in MC3T3-E1 cells including an Src-like kinase-dependent pathway and a protein kinase C (PKC)-dependent mechanism. Functional analyses suggested that these two components are required for optimal DNA synthesis in response to LPA and PGF(2α). These results suggest the implication of two pathways in the stimulation of Erk and cell replication by growth factors acting through Gi and Gq protein-coupled receptors in bone-forming cells.",
author = "J. Caverzasio and G. Palmer and Atsushi Suzuki and Bonjour, {J. P.}",
year = "2000",
month = "1",
day = "1",
doi = "10.1359/jbmr.2000.15.9.1697",
language = "English",
volume = "15",
pages = "1697--1706",
journal = "Journal of Bone and Mineral Research",
issn = "0884-0431",
publisher = "Wiley-Blackwell",
number = "9",

}

TY - JOUR

T1 - Evidence for the involvement of two pathways in activation of extracellular signal-regulated kinase (Erk) and cell proliferation by Gi and Gq protein-coupled receptors in osteoblast-like cells

AU - Caverzasio, J.

AU - Palmer, G.

AU - Suzuki, Atsushi

AU - Bonjour, J. P.

PY - 2000/1/1

Y1 - 2000/1/1

N2 - The mechanisms by which Gi and Gq protein-coupled receptors mediate mitogenic signaling in osteoblast-like cells are unknown and were investigated in MC3T3-E1 cells using specific receptor agonists such as lysophosphatidic acid (LPA) and prostaglandin F(2α) (PGF(2α)). In contrast to their implication in epidermal growth factor (EGF) receptor tyrosine kinase signaling, the adaptor protein Shc, the Grb2/Sos complex, and the small G protein Ras were not involved in the activation of Erk induced by either LPA or PGF(2α) in MC3T3-E1 cells, suggesting that activation of Erk by Gi and Gq protein-coupled receptors is Ras independent in these cells. Using specific kinase inhibitors and kinetic analyses, we provide evidence for two distinct components in the activation of Erk by Gi and Gq protein-coupled receptors in MC3T3-E1 cells including an Src-like kinase-dependent pathway and a protein kinase C (PKC)-dependent mechanism. Functional analyses suggested that these two components are required for optimal DNA synthesis in response to LPA and PGF(2α). These results suggest the implication of two pathways in the stimulation of Erk and cell replication by growth factors acting through Gi and Gq protein-coupled receptors in bone-forming cells.

AB - The mechanisms by which Gi and Gq protein-coupled receptors mediate mitogenic signaling in osteoblast-like cells are unknown and were investigated in MC3T3-E1 cells using specific receptor agonists such as lysophosphatidic acid (LPA) and prostaglandin F(2α) (PGF(2α)). In contrast to their implication in epidermal growth factor (EGF) receptor tyrosine kinase signaling, the adaptor protein Shc, the Grb2/Sos complex, and the small G protein Ras were not involved in the activation of Erk induced by either LPA or PGF(2α) in MC3T3-E1 cells, suggesting that activation of Erk by Gi and Gq protein-coupled receptors is Ras independent in these cells. Using specific kinase inhibitors and kinetic analyses, we provide evidence for two distinct components in the activation of Erk by Gi and Gq protein-coupled receptors in MC3T3-E1 cells including an Src-like kinase-dependent pathway and a protein kinase C (PKC)-dependent mechanism. Functional analyses suggested that these two components are required for optimal DNA synthesis in response to LPA and PGF(2α). These results suggest the implication of two pathways in the stimulation of Erk and cell replication by growth factors acting through Gi and Gq protein-coupled receptors in bone-forming cells.

UR - http://www.scopus.com/inward/record.url?scp=0033843748&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033843748&partnerID=8YFLogxK

U2 - 10.1359/jbmr.2000.15.9.1697

DO - 10.1359/jbmr.2000.15.9.1697

M3 - Article

VL - 15

SP - 1697

EP - 1706

JO - Journal of Bone and Mineral Research

JF - Journal of Bone and Mineral Research

SN - 0884-0431

IS - 9

ER -