MAP kinase activation by mu opioid receptor involves phosphatidylinositol 3-kinase but not the cAMP/PKA pathway

The involvement of protein kinases was studied in mu opioid receptor activa tion of mitogen-activated protein (MAP) kinase using cells transfected with the receptor clone. The cAMP/protein kinase A (PKA) pathway is known to be the major biochemical pathway For mu opioid receptor signaling, However, o ur data showed that stimulating adenylyl cyclase or activating PKA had no e ffect on mu receptor enhancement of MAP kinase activity, suggesting that th e cAMP/PKA. pathway is not involved in mediating the mu receptor activation of MAP, kinase, Inhibition of phosphatidylinositol (PI) 3-kinase reduced m u receptor enhancement of MAP kinase activity, suggesting IPI 3-kinase invo lvement, Together, these results show that crosstalk between the mu opioid receptor and the MAP kinase cascade is not mediated by the cAMP/PKA pathway , but involves PI 3-kinase, (C) 1999 Federation of European Biochemical Soc ieties.