The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Rho and Rho kinase are involved in parathyroid hormone- stimulated protein kinase C alpha translocation and IL-6 promoter activity in osteoblastic cells.

The role of small G-proteins in PTH- stimulated PKC translocation and IL-6 promoter expression in UMR-106 cells was determined. The effects of PTH(1-34) and PTH(3-34) in stimulating PKCalpha translocation and IL-6 were inhibited by agents that interfere with the activity of small G-proteins of the Rho family and with the downstream kinase Rho kinase. INTRODUCTION: Activation of protein kinase C ( PKC) is a signaling mechanism by which parathyroid hormone (PTH) modulates interleukin-6 (IL-6) in osteoblasts, leading to osteoclastogenesis and bone resorption. PKCalpha and PKCbetaI are translocated after treatment with PTH in UMR-106 osteoblastic cells; however, the pathway leading to PKC isozyme translocation is not established. Diacylglycerol (DAG) generation from phospholipase D ( PLD) is one pathway of PKC activation, and PTH- mediated PLD activity is dependent on small G-proteins of the Rho family. This study investigated whether Rho proteins modulate the PKCalpha translocation and IL-6 promoter activity stimulated by PTH in UMR-106 cells. MATERIALS AND METHODS: UMR-106 cells were treated with PTH(1-34) or PTH(3-34). PKC translocation was determined by immunofluorescence, Rho A activation by Rhotekin assay and by translocation assessed by Western blotting in membrane and cytosol fractions, and IL-6 promoter expression by luciferase assay. RESULTS AND CONCLUSIONS: Inhibition of Rho proteins with Clostridium difficile toxin B or inhibition of Rho prenylation with GGTI attenuated PTH(1-34)- and PTH(3-34)- stimulated translocation of endogenous PKCalpha and IL-6 promoter activity. Expression of a constitutively active RhoA (RhoA63L) mimicked the effect of PTH(1-34) or PTH(3-34) to promote membrane localization of PKCalpha, whereas cells expressing a dominant negative RhoA (RhoA19N) did not respond to PTH(1-34) or PTH(3-34). The Rho kinase inhibitor Y27632 attenuated PTH(1-34)- and PTH(3-34)- stimulated PKCalpha translocation and IL-6 promoter activation. Rho seemed to be acting at a step before production of diacylglycerol (DAG), because the stimulation of PKCalpha translocation by the DAG mimetic phorbol 12,13 dibutyrate (PDBu) was unaffected by C. difficile toxin B or Y27632. These results indicate that Rho proteins are an important component of PTH signaling in osteoblastic cells and provide further demonstration of convergence between PKC and small G-protein signaling pathways.[1]


WikiGenes - Universities