%0 Journal Article
%T Evidence for the involvement of Gi2 in activation of extracellular signal-regulated kinases in hepatocytes
%A £¿yvind Melien
%A Thoralf Christoffersen
%A Mouldy Sioud
%J BMC Cell Biology
%D 2001
%I BioMed Central
%R 10.1186/1471-2121-2-13
%X Targeting the Gi2¦Á expression by a specific ribozyme inhibited the PGF2¦Á -induced ERK1/2 activation in hepatocytes. On the other hand a non-cleaving form of the Gi2¦Á ribozyme did not significantly decrease the ERK1/2 activation. In ribozyme-treated cells the Gi2¦Á protein level was reduced, while the Gq¦Á level was not affected thus confirming the specificity of the ribozyme.The present data suggest an important role of Gi2 in PGF2¦Á -induced ERK1/2 signaling in hepatocytes.The extracellular regulated kinases ERK1 (p44mapk) and ERK2 (p42mapk) are believed to be implicated in regulation of cell growth and differentiation [1,2]. They are activated in response to stimulation both of heptahelical G protein coupled receptors (GPCRs) and receptor tyrosine kinases (RTKs). Epidermal growth factor (EGF), hepatocyte growth factor (HGF), PGF2¦Á, norepinephrine, and several other agents activate ERK1/2 in hepatocytes [3,4,5,6]. Furthermore, it was observed in these cells that pretreatment with pertussis toxin (PTX) decreased activation of ERK1/2 in response to various agents acting on RTKs or GPCRs [6,7,8,9]. The data suggest an involvement of Gi protein(s) in the mechanisms of ERK1/2 activation in hepatocytes. However, it is not known which Gi protein(s) that mediate this effect. To approach this issue we have targeted the ¦Á subunit of Gi2 by a catalytic RNA (ribozyme) [10,11]. The effect of the ribozyme on PGF2¦Á -induced ERK1/2 activation, which is strongly sensitive to PTX, was subsequently assessed.Pretreatment of hepatocytes with pertussis toxin [12] was reported to decrease ERK1/2 activation by agents acting both on heptahelical G protein coupled receptors as well as receptor tyrosine kinases [6,7,8]. These observations are summarized in Fig. 1. In addition these data show the persistence with time of the marked inhibitory effect of PTX on ERK1/2 activation induced by PGF2¦Á . The EGF- and HGF-induced responses are on the other hand only partially decreased. These findings sug
%U http://www.biomedcentral.com/1471-2121/2/13