Receptor for activated C kinase 1

Function

RACK1 was originally isolated and identified as an intracellular protein receptor for protein kinase C, noting the significant homology to the beta subunit of heterotrimeric G proteins. Later studies established RACK1, and its yeast homolog Asc1, as a core ribosomal protein of the eukaryotic small (40S) ribosomal subunit. Much of the function of Asc1/RACK1 appears to result from its position on the 'head' of the 40S ribosomal subunit. Asc1/RACK1 participates in several aspects of eukaryotic translation and ribosome quality control, including IRES-mediated translation, non-stop decay, non-functional 18S ribosomal RNA decay, and frameshifting.

Interactions

RACK1 is positioned at the solvent-exposed surface of the 40S ribosomal subunit, where it is held in place through contacts with both the 18S rRNA and other ribosomal proteins, including uS3, uS9, and eS17. Additionally, RACK1 has been shown to interact with:

• AGTRAP
• Androgen receptor,
• CD18,
• CD29
• Cyclin A1
• EIF6,
• FYN,
• IFNAR2,
• Janus kinase 1
• OTUB1,
• P73,
• PDE4D,
• PRKCB1,
• PRKCE,
• PTPRM,
• RAS p21 protein activator 1,
• ST7,
• STAT1,
• Src, and
• Tyrosine kinase 2.

References

References

1. (February 1994). "Cloning of an intracellular receptor for protein kinase C: a homolog of the beta subunit of G proteins". Proceedings of the National Academy of Sciences of the United States of America.
2. (June 1989). "Physical linkage of a guanine nucleotide-binding protein-related gene to the chicken major histocompatibility complex". Proceedings of the National Academy of Sciences of the United States of America.
3. (October 2004). "Identification of the versatile scaffold protein RACK1 on the eukaryotic ribosome by cryo-EM". Nature Structural & Molecular Biology.
4. (September 2004). "Yeast Asc1p and mammalian RACK1 are functionally orthologous core 40S ribosomal proteins that repress gene expression". Molecular and Cellular Biology.
5. (February 2011). "Crystal structure of the eukaryotic 40S ribosomal subunit in complex with initiation factor 1". Science.
6. (March 2009). "Direct link between RACK1 function and localization at the ribosome in vivo". Molecular and Cellular Biology.
7. (November 2014). "RACK1 controls IRES-mediated translation of viruses". Cell.
8. (June 2016). "Ribosome-associated Asc1/RACK1 is required for endonucleolytic cleavage induced by stalled ribosome at the 3' end of nonstop mRNA". Scientific Reports.
9. (December 2017). "ASC1 and RPS3: new actors in 18S nonfunctional rRNA decay". RNA.
10. (May 2015). "Asc1, homolog of human RACK1, prevents frameshifting in yeast by ribosomes stalled at CGA codon repeats". RNA.
11. (January 2002). "Identification and characterization of AGTRAP, a human homolog of murine Angiotensin II Receptor-Associated Protein (Agtrap)". The International Journal of Biochemistry & Cell Biology.
12. (November 2003). "The scaffolding protein RACK1 interacts with androgen receptor and promotes cross-talk through a protein kinase C signaling pathway". The Journal of Biological Chemistry.
13. (January 1998). "Rack1, a receptor for activated protein kinase C, interacts with integrin beta subunit". The Journal of Biological Chemistry.
14. (November 2002). "Activation of Integrin-RACK1/PKCalpha signalling in human articular chondrocyte mechanotransduction". Osteoarthritis and Cartilage.
15. (August 2004). "Identification of interaction partners and substrates of the cyclin A1-CDK2 complex". The Journal of Biological Chemistry.
16. (December 2003). "Release of eIF6 (p27BBP) from the 60S subunit allows 80S ribosome assembly". Nature.
17. (March 2003). "Pituitary adenylate cyclase-activating polypeptide (PACAP(1-38)) enhances N-methyl-D-aspartate receptor function and brain-derived neurotrophic factor expression via RACK1". The Journal of Biological Chemistry.
18. (April 2002). "NMDA receptor function is regulated by the inhibitory scaffolding protein, RACK1". Proceedings of the National Academy of Sciences of the United States of America.
19. (November 2000). "Receptor for activated C-kinase (RACK-1), a WD motif-containing protein, specifically associates with the human type I IFN receptor". Journal of Immunology.
20. (March 2009). "Structural basis and specificity of human otubain 1-mediated deubiquitination". The Biochemical Journal.
21. (May 2003). "Function of p73, not of p53, is inhibited by the physical interaction with RACK1 and its inhibitory effect is counteracted by pRB". Oncogene.
22. (May 1999). "The RACK1 signaling scaffold protein selectively interacts with the cAMP-specific phosphodiesterase PDE4D5 isoform". The Journal of Biological Chemistry.
23. (July 2001). "Identification of a surface on the beta-propeller protein RACK1 that interacts with the cAMP-specific phosphodiesterase PDE4D5". Cellular Signalling.
24. (September 1999). "Coordinated movement of RACK1 with activated betaIIPKC". The Journal of Biological Chemistry.
25. (June 2002). "Protein kinase C epsilon-dependent regulation of cystic fibrosis transmembrane regulator involves binding to a receptor for activated C kinase (RACK1) and RACK1 binding to Na+/H+ exchange regulatory factor". The Journal of Biological Chemistry.
26. (March 2002). "Expression of the receptor protein-tyrosine phosphatase, PTPmu, restores E-cadherin-dependent adhesion in human prostate carcinoma cells". The Journal of Biological Chemistry.
27. (May 2001). "The PTPmu protein-tyrosine phosphatase binds and recruits the scaffolding protein RACK1 to cell-cell contacts". The Journal of Biological Chemistry.
28. (May 2001). "RACK1, a protein kinase C scaffolding protein, interacts with the PH domain of p120GAP". Biochemical and Biophysical Research Communications.
29. (June 2003). "ST7 is a novel low-density lipoprotein receptor-related protein (LRP) with a cytoplasmic tail that interacts with proteins related to signal transduction pathways". Biochemistry.
30. (June 2001). "The WD motif-containing protein receptor for activated protein kinase C (RACK1) is required for recruitment and activation of signal transducer and activator of transcription 1 through the type I interferon receptor". The Journal of Biological Chemistry.
31. (September 2003). "The WD motif-containing protein RACK-1 functions as a scaffold protein within the type I IFN receptor-signaling complex". Journal of Immunology.
32. (June 1998). "RACK1, a receptor for activated C kinase and a homolog of the beta subunit of G proteins, inhibits activity of src tyrosine kinases and growth of NIH 3T3 cells". Molecular and Cellular Biology.