AKAPs (A-kinase anchoring proteins) and molecules that compose their G-protein-coupled receptor signalling complexes [Review]

摘要

Cell signalling, mediated via GPCRs (G-protein-Coupled receptors) is a major paradigm in biology, involving the assembly of receptors, G-proteins. effectors and downstream elements into complexes that approach in design 'solid-state' signalling devices. Scaffold molecules. Such as the AKAPs (A-kinase anchoring proteins), were discovered more than a decade ago and represent dynamic platforms, enabling multivalent signalling. AKAP79 and AKAP250 were the first to be shown to bind to membrane-embedded GPCRs. orchestrating the interactions of Various protein kinases (including tyrosine kinases), protein phosphatases (e.g. calcinCLH-in) and cytoskeletal elements with Lit least one member of the, superfamily of GPCRs, the prototypical beta(2)-adrenergic receptor. In this review, the multivalent interactions of AKAP250 with the cell membrane, receptor, cytoskeleton and constituent components are detailed, providing a working model for AKAP-based GPCR signalling complexes. Dynamic regulation of the AKAP-receptor complex is mediated by ordered protein phosphorylation.