SIGNAL-TRANSDUCTION PATHWAY OF PROLACTIN IN RAT-LIVER

We previously reported that a single intraperitoneal injection of prol actin (PRL) in female adult rats rapidly and transiently activates mit ogen-activated protein kinase (MAPK) in the liver (Piccoletti et al., (1994) Biochem. J. 303; 429-423). Here we analysed the PRL signalling pathway that accounts for MAPK activation. We found that total liver M APK kinase-1 phosphorylating activity and Raf-1 activity significantly increase after PRL treatment, following a time course that accounts f or the activation of MAPK. We also identified a significant increase i n the phosphotyrosine content of the 52 kDa Shc protein, accompanied b y an increase in Shc coimmunoprecipitated Grb2, which suggests the Ras involvement by PRL. We found that Janus kinase (JAK)2 tyrosine kinase , which appears constitutively associated with the PRL receptor expres sed in the liver, is activated and associated with Shc proteins after in vivo PRL treatment. Taken together our data provide evidence that i n vivo PRL activates the Shc-Ras-Raf-MAPK cascade in the liver by the involvement of JAK2 and suggests the possibility that the liver short form of PRL receptor plays a role in triggering this signalling pathwa y. (C) 1997 Elsevier Science Ireland Ltd.