Regulation of eukaryotic translation by the RACK1 protein: a platform for signalling molecules on the ribosome

Abstract

The receptor for activated C-kinase (RACK1) is a scaffold protein that is able to interact simultaneously with several signalling molecules. It binds to protein kinases and membrane-bound receptors in a regulated fashion. Interestingly, RACK1 is also a constituent of the eukaryotic ribosome, and a recent cryo-electron microscopy study localized it to the head region of the 40S subunit in the vicinity of the messenger RNA (mRNA) exit channel. RACK1 recruits activated protein kinase C to the ribosome, which leads to the stimulation of translation through the phosphorylation of initiation factor 6 and, potentially, of mRNAassociated proteins. RACK1 therefore links signal-transduction pathways directly to the ribosome, which allows translation to be regulated in response to cell stimuli. In addition, the fact that RACK1 associates with membrane-bound receptors indicates that it promotes the docking of ribosomes at sites where local translation is required, such as focal adhesions.

High heterogeneity within the ribosomal proteins of the Arabidopsis thaliana 80S ribosome

“…RACK1 is a newly discovered ribosomal protein, present in all eukaryotic genomes and has so far been demonstrated to be present in the small subunit of yeast and human ribosomes (Link et al, 1999;Ceci et al, 2003; reviewed by Nilsson et al, 2004). RACK1 has been shown to interact with a number of different signalling molecules, such as Src, intergrin-b and PKC, and through this interaction is thought to mediate translation regulation.…”

Eukaryote-specific extensions in ribosomal proteins of the small subunit: Structure and function

“…6,73 RACK1 is known to play an important role in numerous biological responses/signaling events, in turn involving its interaction with kinases and receptors in a regulated manner. 74 Therefore, interaction between uS3 and Asc1 might act as an important link between translational control of gene expression and cellular signaling. 74 Whether disruption of uS3-Asc1/RACK1 might abrogate this link remains to be tested.…”

“…74 Therefore, interaction between uS3 and Asc1 might act as an important link between translational control of gene expression and cellular signaling. 74 Whether disruption of uS3-Asc1/RACK1 might abrogate this link remains to be tested.…”

Phosphorylation of RACK1 in plants

“…[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.…”

“…This also opens up a few more questions: (1) How RACK1 phosphorylation by WNK8 is regulated? (2) What is the phosphatase that counteracts RACK1 phosphorylation by WNK8? (3) Is RACK1 protein subject to Tyr phosphorylation by an unidentified Tyr kinase?…”