An emerging class of A-Kinase Anchoring Proteins are R2D2-like
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Abstract
Abstract
A precise cellular response to both internal and external stimuli is crucial for the normal growth and development of all organisms. Almost all such responses are now known to be carried out by signal transduction pathways that involve signaling molecules such as receptors, second messengers, modifiers, effectors such as kinases, transcription factors, etc. Of critical importance are the modifiers such as scaffold proteins that impart spatial and temporal regulatory features to the response. A-Kinase Anchoring Proteins (AKAPs) are one such well-studied scaffold proteins that bind to cAMP-dependent protein kinase (PKA) and an array of signaling proteins. AKAPs are known to amplify, accelerate, localize and bring about specificity to the response. The AKAP-PKA complex is well studied and it has been found that regulatory subunits of PKA bind to the amphipathic helix of the AKAPs via their dimerization and docking (D/D) domains with what is commonly referred to as the RII-fold. This domain and fold is a characteristic feature of all the known regulatory subunits of PKA. However, recently, some molecules with an RII-fold have become known to bind to the amphipathic helices of AKAPs via their D/D-like domains; among others, these include several sperm proteins such as ropporin, AKAP-associated sperm protein (ASP), Sperm Protein-17 (SP-17) and fibrosheathin II (FSII) and others like DPY-30, RSP9, RSP11 and Myc-Binding Protein-1. The list of these types of proteins is growing and is referred to here as the atypical RII proteins (R2D2 proteins).
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