Compartmentalization of protein kinase A signaling by the heterotrimeric G protein Go

G(o), a member of the G(o/i) family, is the most abundant heterotrimeric G protein in brain. Most functions of G(o) are mediated by the G(beta gamma) dimer; effector(s) for its beta-subunit have not been clearly defined. Here we report that G(o alpha) interacts directly with cAMP-dependent protein kinase (PKA) through its GTPase domain. This interaction did not inhibit the kinase function of PKA but interfered with nuclear translocation of PKA while sparing its cytosolic function. This regulatory mechanism by which G(o) bifurcates PKA signaling may provide insights into how G(o) regulates complex processes such as neuritogenesis, synaptic plasticity, and cell transformation.