RACK1, A multifaceted scaffolding protein: Structure and function

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.

The Association of Receptor of Activated Protein Kinase C 1(RACK1) with Infectious Bursal Disease Virus Viral Protein VP5 and Voltage-dependent Anion Channel 2 (VDAC2) Inhibits Apoptosis and Enhances Viral Replication

“…RACK1, also named guanine nucleotide binding protein subunit ␤ 2 like 1 (GNB2L1), has been identified as a WD40 motif protein that exists ubiquitously in the macromolecular complexes (40). The conserved seven-blade propeller structure gives RACK1 a strong protein binding capacity.…”

“…RACK1 is highly conserved in all species, such as human, mice, chicken, canine, and swine (41). It has been reported that RACK1 can interact with multiple proteins, such as Src (42), Hif-1 ␣ (43), androgen receptor (44), JAKs (45), and STATs (46), suggesting that RACK1 may act as a scaffolding protein, recruiting various proteins, providing a platform for protein interaction, and playing a critical role in different aspects of cell regulation (40).…”

Phosphorylation of RACK1 in plants

“…The seven blade propeller structure of RACK1 allows it to function as a signaling hub. 4 The protein sequences and the structure of RACK1 are conserved in plants. 8,9 Similar to mammalian RACK1, plant RACK1 interacts with a large group of proteins 10,11 and is involved in diverse biological processes, ranging from seed germination, leaf and root development to flowering, 8,12 and is also involved in responses to plant hormones, 8,13 and biotic and abiotic stresses.…”

“…Studies using mammalian cells suggested a few possible mechanisms including translocation of RACK1 protein from one cellular compartment to another, formation of protein complex with other scaffolding proteins and contribution to transcription and translation. 4,6 These abilities of RACK1 lead to its temporal and spatial regulation of diverse signal transduction events. Emerging evidence suggest that the transcriptional and translational modification of RACK1 itself also play an important role in regulating its function.…”

“…[1][2][3][4][5][6][7] RACK1 protein contains a 7 tryptophan-aspartic acid repeat domain (WD40) similar to that in the heterotrimeric GTP-binding protein b subunit. The seven blade propeller structure of RACK1 allows it to function as a signaling hub.…”