The Liver Response to in Vivo Heat Shock Involves the Activation of Map Kinases and Raf and the Tyrosine Phosphorylation of Shc Proteins

Abstract

We have investigated the mechanisms of signal transduction in the response of liver to heat shock in vivo. By immunoblot experiments we have shown that heat shock decreases the electrophoretic mobility of the 40 and 43 kDa mitogen activated protein kinases (MAPKs) and we have found a significant increase of MAPK activity measured as phosphotransferase capacity of both cytosolic extracts and MAPK immunoprecipitates. To elucidate the signalling pathway which accounts for MAPK activation, we focused our attention on its upstream factors, Raf and Res. We have shown that, heat shock activates Raf-1 kinase and causes an increase in phosphotyrosine content of the 52 kDa She protein accompanied by an increment in the amount of coimmunoprecipitated Grb2. These findings provide the first evidence that the Ras-Raf-MAPK pathway is activated in liver during heat shock in vivo.