AKAPs (A-kinase anchoring proteins) are members of a diverse family of scaffold proteins that minimally possess a characteristic binding domain for the RI/RII regulatory subunit of protein kinase A and play critical roles in establishing spatial constraints for multivalent signalling assemblies. Especially for G-protein-coupled receptors, the AKAPs provide an organizing centre about which various protein kinases and phosphatases can be assembled to create solid-state signalling devices that can signal, be modulated and trafficked within the cell. The structure of AKAP250 (also known as gravin or AKAP12), based on analyses of milligram quantities of recombinant protein expressed in Escherichia coli, suggests that the AKAP is probably an unordered scaffold, acting as a necklace on which 'jewels' of structure-function (e.g. the RII-binding domain) that provide docking sites on which signalling components can be assembled. Recent results suggest that AKAP250 provides not only a 'tool box' for assembling signalling elements, but may indeed provide a basis for spatial constraint observed for many signalling paradigms. The spatial dimension of the integration of cell signalling will probably reflect many functions performed by members of the AKAP family.

Wnt proteins signal via cell surface receptors termed Frizzleds. Frizzleds display many properties characteristic of members of the superfamily of G-protein-coupled receptors, including heptihelical hydropathy plots; an exofacial N-terminal region that is glycosylated; a cytoplasmic C-terminal region that includes canonical motifs for phosphorylation by protein kinase A, protein kinase C and casein kinase II; cytoplasmic domains that couple to heterotrimeric G proteins, as evidenced by a GTP-shift in receptor affinity; receptor-mediated responses sensitive to depletion of specific G protein subunits and receptor-mediated responses sensitive to bacterial toxins that target G proteins. Evidence from a variety of developmental systems demonstrates Wnt-Frizzled (Fz) signaling via pathways other than the Wnt/beta-catenin pathway linked to transcription controlled by Lef/Tcf. Prominent among these additional pathways is a Wnt-Fz pathway regulating intracellular [Ca(++)] and cyclic GMP levels. The essential role of heterotrimeric G proteins in Wnt-Fz signaling is highlighted.