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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
Author(s) -
Caverzasio Joseph,
Palmer Gaby,
Suzuki Atsushi,
Bonjour JeanPhilippe
Publication year - 2000
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1359/jbmr.2000.15.9.1697
Subject(s) - microbiology and biotechnology , mapk/erk pathway , signal transduction , protein kinase a , lysophosphatidic acid , protein kinase c , grb2 , receptor , g protein coupled receptor , biology , signal transducing adaptor protein , tyrosine kinase , epidermal growth factor , kinase , chemistry , biochemistry
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.