title: Interplay of PKA and Rac: fine-tuning of Rac localization and signaling.
abstract: Cellular membrane receptors sense environmental changes and relay the reshaped signal through spatially and temporally organized protein-protein interactions (PPI). Many of such PPI are transient and occur in a certain cell-dependent context. Molecular switches such as kinases and GTPases are engaged in versatile PPI. Recently, we have identified dynamic interaction and reciprocal regulation of cAMP-dependent protein kinase A (PKA) and Rho-GTPase Rac signaling. We demonstrated that GTP-activated Rac acts as a dual kinase-tuning scaffold for p21-activated kinase (PAK) and PKA activities. We showed that receptor-triggered PKA trans-phosphorylation of GTP-Rac-organized PAK contributes to elevations of nuclear Erk1/2 signaling and proliferation. We discuss these recent observations and we provide additional insights how the cAMP-PKA axis might also participate in the regulation of Rac localization.
authors: Institute of Biochemistry; University of Innsbruck; Innsbruck, Austria.
authors: Verena A
authors: VA
authors: Bachmann
authors: Institute of Biochemistry; University of Innsbruck; Innsbruck, Austria.
authors: Klaus
authors: K
authors: Bister
authors: Institute of Biochemistry; University of Innsbruck; Innsbruck, Austria.
authors: Eduard
authors: E
authors: Stefan
mesh_terms: D005260:Female; D006801:Humans; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000502:physiology; D009097:Multienzyme Complexes / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
chemical_list: D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D009097:Multienzyme Complexes; D020830:rac1 GTP-Binding Protein
keywords: PKA; Rac; cAMP; cross talk; kinase; p21-activated kinase; proliferation; scaffold; translocation