scholarly journals Inverse agonist abolishes desensitization of a constitutively active mutant of thyrotropin-releasing hormone receptor: role of cellular calcium and protein kinase C

1999 ◽  
Vol 126 (5) ◽  
pp. 1097-1106 ◽  
Author(s):  
Hagit Grimberg ◽  
Ilona Zaltsman ◽  
Monica Lupu-Meiri ◽  
Marvin C Gershengorn ◽  
Yoram Oron
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Hormone Receptor ◽  
Inverse Agonist ◽  
Thyrotropin Releasing Hormone ◽  
Releasing Hormone ◽  
Cellular Calcium ◽  
Kinase C ◽  
Constitutively Active

scholarly journals Continuous Activation of Gαq in Osteoblasts Results in Osteopenia through Impaired Osteoblast Differentiation

2007 ◽  
Vol 282 (49) ◽  
pp. 35757-35764 ◽  
Author(s):  
Naoshi Ogata ◽  
Hiroshi Kawaguchi ◽  
Ung-il Chung ◽  
Sanford I. Roth ◽  
Gino V. Segre
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Transgenic Mice ◽  
Trabecular Thickness ◽  
Kinase C ◽  
Protein Kinase C Inhibitor ◽  
Skeletal Homeostasis ◽  
Trabecular Bones ◽  
Constitutively Active

We explored the role of Gαq-mediated signaling on skeletal homeostasis by selectively expressing a constitutively active Gαq (mutation of Q209L) in osteoblasts. Continuous signaling via Gαq in mouse osteoblastic MC3T3-E1 cells impaired differentiation. Mice that expressed the constitutively active Gαq transgene in cells of the osteoblast lineage exhibited severe osteopenia in cortical and trabecular bones. Osteoblast number, bone volume, and trabecular thickness were reduced in transgenic mice, but the osteoclasts were unaffected. Osteoblasts from transgenic mice showed impaired differentiation and matrix formation. In the presence of a protein kinase C inhibitor GF109203X, this impairment was not seen, indicating mediation by the protein kinase C pathway. We propose that continuous activation of the Gαq signal in osteoblasts plays a crucial, previously unrecognized role in bone formation.

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