Abstract
The Receptor for Activated C Kinase 1 (RACK1) is a member of the tryptophan-aspartate repeat (WD-repeat) family of proteins and shares significant homology to the β subunit of G-proteins (Gβ). RACK1 adopts a seven-bladed β-propeller structure which facilitates protein binding. RACK1 has a significant role to play in shuttling proteins around the cell, anchoring proteins at particular locations and in stabilising protein activity. It interacts with the ribosomal machinery, with several cell surface receptors and with proteins in the nucleus. As a result, RACK1 is a key mediator of various pathways and contributes to numerous aspects of cellular function. Here, we discuss RACK1 gene and structure and its role in specific signaling pathways, and address how posttranslational modifications facilitate subcellular location and translocation of RACK1. This review condenses several recent studies suggesting a role for RACK1 in physiological processes such as development, cell migration, central nervous system (CN) function and circadian rhythm as well as reviewing the role of RACK1 in disease.
Highlights
The WD-repeat family of proteins The tryptophan, aspartic acid repeat
We previously reported that upon activation of PKA by the adenylate cyclase forskolin, or the pituitary adenylate cyclase activating peptide (PACAP), Receptor for Activated C Kinase 1 (RACK1) translocates to the nucleus where it mediates the expression of the brain-derived neurotrophic factor (BDNF) [56,106] (Figure 4)
One possibility is that the different intracellular compartmentalization of RACK1 in different cell types and regions allows the scaffolding protein to interact with multiple proteins and to regulate various functions in a cell specific manner
Summary
The WD-repeat family of proteins The tryptophan, aspartic acid repeat A binding site for the glucocorticoid receptor is present in the GNB2L1 promoter [63], suggesting a mechanism by which RACK1 expression levels may change with aging This is significant given that RACK1 affects the subcellular distribution and function of numerous proteins and, as a result, plays an essential role in regulating signaling pathways in many key biological processes [46,47]. This GH interaction plays an important role in defining the trajectory of the inter-blade D-A loop which hosts the GH dipeptide and in stabilising the propeller structure.
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