Receptor for activated C kinase 1

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Receptor for activated C kinase 1 (RACK1), also known as guanine nucleotide-binding protein subunit beta-2-like 1 (GNB2L1), is a 35 kDa protein that in humans is encoded by the RACK1 gene.[1][2]

## Contents

* 1 Function
* 2 Interactions
* 3 See also
* 4 References
* 5 Further reading

## Function

[edit | edit source]

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.[1] Later studies established RACK1, and its yeast homolog Asc1, as a core ribosomal protein of the eukaryotic small (40S) ribosomal subunit.[3][4][5] Much of the function of Asc1/RACK1 appears to result from its position on the 'head' of the 40S ribosomal subunit.[6] Asc1/RACK1 participates in several aspects of eukaryotic translation and ribosome quality control, including IRES-mediated translation[7], non-stop decay[8], non-functional 18S ribosomal RNA decay[9], and frameshifting[10].

## Interactions

[edit | edit source]

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[11]
* Androgen receptor,[12]
* CD18,[13]
* CD29[13][14]
* Cyclin A1[15]
* EIF6,[16]
* FYN,[17][18]
* IFNAR2,[19][20]
* Janus kinase 1[21]
* OTUB1,[22]
* P73,[23]
* PDE4D,[24][25]
* PRKCB1,[26]
* PRKCE,[27]
* PTPRM,[28][29]
* RAS p21 protein activator 1,[30]
* ST7,[31]
* STAT1,[19][21]
* Src,[32] and
* Tyrosine kinase 2.[21]

## See also

[edit | edit source]

* Eukaryotic small ribosomal subunit (40S)
* Protein kinase C
* Heterotrimeric G protein

## References

[edit | edit source]

1. ↑ 1.0 1.1 Ron D, Chen CH, Caldwell J, Jamieson L, Orr E, Mochly-Rosen D (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. 91 (3): 839–43. doi:10.1073/pnas.91.3.839. PMC 521407. PMID 8302854.
2. ↑ Guillemot F, Billault A, Auffray C (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. 86 (12): 4594–8. doi:10.1073/pnas.86.12.4594. PMC 287317. PMID 2499885.
3. ↑ Sengupta J, Nilsson J, Gursky R, Spahn CM, Nissen P, Frank J (October 2004). "Identification of the versatile scaffold protein RACK1 on the eukaryotic ribosome by cryo-EM". Nature Structural & Molecular Biology. 11 (10): 957–62. doi:10.1038/nsmb822. PMID 15334071.
4. ↑ Gerbasi VR, Weaver CM, Hill S, Friedman DB, Link AJ (September 2004). "Yeast Asc1p and mammalian RACK1 are functionally orthologous core 40S ribosomal proteins that repress gene expression". Molecular and Cellular Biology. 24 (18): 8276–87. doi:10.1128/mcb.24.18.8276-8287.2004. PMC 515043. PMID 15340087.
5. ↑ Rabl J, Leibundgut M, Ataide SF, Haag A, Ban N (February 2011). "Crystal structure of the eukaryotic 40S ribosomal subunit in complex with initiation factor 1". Science. 331 (6018): 730–6. doi:10.1126/science.1198308. PMID 21205638.
6. ↑ Coyle SM, Gilbert WV, Doudna JA (March 2009). "Direct link between RACK1 function and localization at the ribosome in vivo". Molecular and Cellular Biology. 29 (6): 1626–34. doi:10.1128/mcb.01718-08. PMC 2648249. PMID 19114558.
7. ↑ Majzoub K, Hafirassou ML, Meignin C, Goto A, Marzi S, Fedorova A, Verdier Y, Vinh J, Hoffmann JA, Martin F, Baumert TF, Schuster C, Imler JL (November 2014). "RACK1 controls IRES-mediated translation of viruses". Cell. 159 (5): 1086–1095. doi:10.1016/j.cell.2014.10.041. PMC 4243054. PMID 25416947.
8. ↑ Ikeuchi K, Inada T (June 2016). "Ribosome-associated Asc1/RACK1 is required for endonucleolytic cleavage induced by stalled ribosome at the 3' end of nonstop mRNA". Scientific Reports. 6 (1): 28234. doi:10.1038/srep28234. PMC 4911565. PMID 27312062.
9. ↑ Limoncelli KA, Merrikh CN, Moore MJ (December 2017). "ASC1 and RPS3: new actors in 18S nonfunctional rRNA decay". RNA. Cold Spring Harbor Laboratory. 23 (12): 1946–1960. doi:10.1261/rna.061671.117. PMC 5689013. PMID 28956756.
10. ↑ Wolf AS, Grayhack EJ (May 2015). "Asc1, homolog of human RACK1, prevents frameshifting in yeast by ribosomes stalled at CGA codon repeats". RNA. 21 (5): 935–45. doi:10.1261/rna.049080.114. PMC 4408800. PMID 25792604.
11. ↑ Wang W, Huang Y, Zhou Z, Tang R, Zhao W, Zeng L, Xu M, Cheng C, Gu S, Ying K, Xie Y, Mao Y (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. 34 (1): 93–102. doi:10.1016/s1357-2725(01)00094-2. PMID 11733189.
12. ↑ Rigas AC, Ozanne DM, Neal DE, Robson CN (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. 278 (46): 46087–93. doi:10.1074/jbc.M306219200. PMID 12958311.
13. ↑ 13.0 13.1 Liliental J, Chang DD (January 1998). "Rack1, a receptor for activated protein kinase C, interacts with integrin beta subunit". The Journal of Biological Chemistry. 273 (4): 2379–83. doi:10.1074/jbc.273.4.2379. PMID 9442085.
14. ↑ Lee HS, Millward-Sadler SJ, Wright MO, Nuki G, Al-Jamal R, Salter DM (November 2002). "Activation of Integrin-RACK1/PKCalpha signalling in human articular chondrocyte mechanotransduction". Osteoarthritis and Cartilage. 10 (11): 890–7. doi:10.1053/joca.2002.0842. PMID 12435334.
15. ↑ Diederichs S, Bäumer N, Ji P, Metzelder SK, Idos GE, Cauvet T, Wang W, Möller M, Pierschalski S, Gromoll J, Schrader MG, Koeffler HP, Berdel WE, Serve H, Müller-Tidow C (August 2004). "Identification of interaction partners and substrates of the cyclin A1-CDK2 complex". The Journal of Biological Chemistry. 279 (32): 33727–41. doi:10.1074/jbc.M401708200. PMID 15159402.
16. ↑ Ceci M, Gaviraghi C, Gorrini C, Sala LA, Offenhäuser N, Marchisio PC, Biffo S (December 2003). "Release of eIF6 (p27BBP) from the 60S subunit allows 80S ribosome assembly". Nature. 426 (6966): 579–84. doi:10.1038/nature02160. PMID 14654845.
17. ↑ Yaka R, He DY, Phamluong K, Ron D (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. 278 (11): 9630–8. doi:10.1074/jbc.M209141200. PMID 12524444.
18. ↑ Yaka R, Thornton C, Vagts AJ, Phamluong K, Bonci A, Ron D (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. 99 (8): 5710–5. doi:10.1073/pnas.062046299. PMC 122836. PMID 11943848.
19. ↑ 19.0 19.1 Usacheva A, Smith R, Minshall R, Baida G, Seng S, Croze E, Colamonici O (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. 276 (25): 22948–53. doi:10.1074/jbc.M100087200. PMID 11301323.
20. ↑ Croze E, Usacheva A, Asarnow D, Minshall RD, Perez HD, Colamonici O (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. 165 (9): 5127–32. doi:10.4049/jimmunol.165.9.5127. PMID 11046044.
21. ↑ 21.0 21.1 21.2 Usacheva A, Tian X, Sandoval R, Salvi D, Levy D, Colamonici OR (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. 171 (6): 2989–94. doi:10.4049/jimmunol.171.6.2989. PMID 12960323.
22. ↑ Edelmann MJ, Iphöfer A, Akutsu M, Altun M, di Gleria K, Kramer HB, Fiebiger E, Dhe-Paganon S, Kessler BM (March 2009). "Structural basis and specificity of human otubain 1-mediated deubiquitination". The Biochemical Journal. 418 (2): 379–90. doi:10.1042/BJ20081318. PMID 18954305.
23. ↑ Ozaki T, Watanabe K, Nakagawa T, Miyazaki K, Takahashi M, Nakagawara A (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 (21): 3231–42. doi:10.1038/sj.onc.1206382. PMID 12761493.
24. ↑ Yarwood SJ, Steele MR, Scotland G, Houslay MD, Bolger GB (May 1999). "The RACK1 signaling scaffold protein selectively interacts with the cAMP-specific phosphodiesterase PDE4D5 isoform". The Journal of Biological Chemistry. 274 (21): 14909–17. doi:10.1074/jbc.274.21.14909. PMID 10329691.
25. ↑ Steele MR, McCahill A, Thompson DS, MacKenzie C, Isaacs NW, Houslay MD, Bolger GB (July 2001). "Identification of a surface on the beta-propeller protein RACK1 that interacts with the cAMP-specific phosphodiesterase PDE4D5". Cellular Signalling. 13 (7): 507–13. doi:10.1016/s0898-6568(01)00167-x. PMID 11516626.
26. ↑ Ron D, Jiang Z, Yao L, Vagts A, Diamond I, Gordon A (September 1999). "Coordinated movement of RACK1 with activated betaIIPKC". The Journal of Biological Chemistry. 274 (38): 27039–46. doi:10.1074/jbc.274.38.27039. PMID 10480917.
27. ↑ Liedtke CM, Yun CH, Kyle N, Wang D (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. 277 (25): 22925–33. doi:10.1074/jbc.M201917200. PMID 11956211.
28. ↑ Hellberg CB, Burden-Gulley SM, Pietz GE, Brady-Kalnay SM (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. 277 (13): 11165–73. doi:10.1074/jbc.M112157200. PMID 11801604.
29. ↑ Mourton T, Hellberg CB, Burden-Gulley SM, Hinman J, Rhee A, Brady-Kalnay SM (May 2001). "The PTPmu protein-tyrosine phosphatase binds and recruits the scaffolding protein RACK1 to cell-cell contacts". The Journal of Biological Chemistry. 276 (18): 14896–901. doi:10.1074/jbc.M010823200. PMID 11278757.
30. ↑ Koehler JA, Moran MF (May 2001). "RACK1, a protein kinase C scaffolding protein, interacts with the PH domain of p120GAP". Biochemical and Biophysical Research Communications. 283 (4): 888–95. doi:10.1006/bbrc.2001.4889. PMID 11350068.
31. ↑ Battle MA, Maher VM, McCormick JJ (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. 42 (24): 7270–82. doi:10.1021/bi034081y. PMID 12809483.
32. ↑ Chang BY, Conroy KB, Machleder EM, Cartwright CA (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. 18 (6): 3245–56. doi:10.1128/mcb.18.6.3245. PMC 108906. PMID 9584165.

## Further reading

[edit | edit source]

* Liu YV, Semenza GL (March 2007). "RACK1 vs. HSP90: competition for HIF-1 alpha degradation vs. stabilization". Cell Cycle. 6 (6): 656–9. doi:10.4161/cc.6.6.3981. PMID 17361105.
* Mochly-Rosen D, Miller KG, Scheller RH, Khaner H, Lopez J, Smith BL (September 1992). "p65 fragments, homologous to the C2 region of protein kinase C, bind to the intracellular receptors for protein kinase C". Biochemistry. 31 (35): 8120–4. doi:10.1021/bi00150a003. PMID 1326322.
* Dawson SJ, White LA (May 1992). "Treatment of Haemophilus aphrophilus endocarditis with ciprofloxacin". The Journal of Infection. 24 (3): 317–20. doi:10.1016/S0163-4453(05)80037-4. PMID 1602151.
* Pumiglia KM, LeVine H, Haske T, Habib T, Jove R, Decker SJ (June 1995). "A direct interaction between G-protein beta gamma subunits and the Raf-1 protein kinase". The Journal of Biological Chemistry. 270 (24): 14251–4. doi:10.1074/jbc.270.24.14251. PMID 7782277.
* Maruyama K, Sugano S (January 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
* Disatnik MH, Hernandez-Sotomayor SM, Jones G, Carpenter G, Mochly-Rosen D (January 1994). "Phospholipase C-gamma 1 binding to intracellular receptors for activated protein kinase C". Proceedings of the National Academy of Sciences of the United States of America. 91 (2): 559–63. doi:10.1073/pnas.91.2.559. PMC 42988. PMID 8290562.
* Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (October 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
* Liliental J, Chang DD (January 1998). "Rack1, a receptor for activated protein kinase C, interacts with integrin beta subunit". The Journal of Biological Chemistry. 273 (4): 2379–83. doi:10.1074/jbc.273.4.2379. PMID 9442085.
* Chang BY, Conroy KB, Machleder EM, Cartwright CA (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. 18 (6): 3245–56. doi:10.1128/mcb.18.6.3245. PMC 108906. PMID 9584165.
* Rietzler M, Bittner M, Kolanus W, Schuster A, Holzmann B (October 1998). "The human WD repeat protein WAIT-1 specifically interacts with the cytoplasmic tails of beta7-integrins". The Journal of Biological Chemistry. 273 (42): 27459–66. doi:10.1074/jbc.273.42.27459. PMID 9765275.
* Shimohama S, Kamiya S, Taniguchi T, Kimura J (December 1998). "Intracellular receptors for activated C-kinase in the postmortem human brain: no alteration in Alzheimer disease". Alzheimer Disease and Associated Disorders. 12 (4): 384–6. doi:10.1097/00002093-199812000-00022. PMID 9876970.
* Yarwood SJ, Steele MR, Scotland G, Houslay MD, Bolger GB (May 1999). "The RACK1 signaling scaffold protein selectively interacts with the cAMP-specific phosphodiesterase PDE4D5 isoform". The Journal of Biological Chemistry. 274 (21): 14909–17. doi:10.1074/jbc.274.21.14909. PMID 10329691.
* Ron D, Jiang Z, Yao L, Vagts A, Diamond I, Gordon A (September 1999). "Coordinated movement of RACK1 with activated betaIIPKC". The Journal of Biological Chemistry. 274 (38): 27039–46. doi:10.1074/jbc.274.38.27039. PMID 10480917.
* Geijsen N, Spaargaren M, Raaijmakers JA, Lammers JW, Koenderman L, Coffer PJ (September 1999). "Association of RACK1 and PKCbeta with the common beta-chain of the IL-5/IL-3/GM-CSF receptor". Oncogene. 18 (36): 5126–30. doi:10.1038/sj.onc.1202896. PMID 10490850.
* Smith PR, de Jesus O, Turner D, Hollyoake M, Karstegl CE, Griffin BE, Karran L, Wang Y, Hayward SD, Farrell PJ (April 2000). "Structure and coding content of CST (BART) family RNAs of Epstein-Barr virus". Journal of Virology. 74 (7): 3082–92. doi:10.1128/JVI.74.7.3082-3092.2000. PMC 111807. PMID 10708423.
* Ellis JH, Ashman C, Burden MN, Kilpatrick KE, Morse MA, Hamblin PA (June 2000). "GRID: a novel Grb-2-related adapter protein that interacts with the activated T cell costimulatory receptor CD28". Journal of Immunology. 164 (11): 5805–14. doi:10.4049/jimmunol.164.11.5805. PMID 10820259.
* Croze E, Usacheva A, Asarnow D, Minshall RD, Perez HD, Colamonici O (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. 165 (9): 5127–32. doi:10.4049/jimmunol.165.9.5127. PMID 11046044.
* Hartley JL, Temple GF, Brasch MA (November 2000). "DNA cloning using in vitro site-specific recombination". Genome Research. 10 (11): 1788–95. doi:10.1101/gr.143000. PMC 310948. PMID 11076863.

* v
* t
* e

Protein biosynthesis: translation (bacterial, archaeal, eukaryotic)

Proteins|

| Initiation factor|

| Bacterial|

* PIF-1
* PIF-2
* PIF-3

|

Archaeal|

* aIF1
* aIF2
* aIF5
* aIF6

Eukaryotic|

| eIF1|

* eIF1
* EIF1AX
* AY
* 1B

|

eIF2|

* EIF2S1
* EIF2S2
* EIF2S3
* EIF2B1
* EIF2B2
* EIF2B3
* EIF2B4
* EIF2B5
* EIF-2 kinase
* eIF2A
* eIF2D

eIF3|

* EIF3A
* B
* C
* D
* E
* F
* G
* H
* I
* J
* K
* L
* M

eIF4|

* EIF4A2
* A3
* B
* E1
* E2
* E3
* G1
* G2
* G3
* H

eIF5|

* EIF5
* EIF5A
* A2
* 5B

eIF6|

* EIF6

Elongation factor|

| Bacterial|

* EF-Tu
* EF-Ts
* EF-G

|

Archaeal|

* aEF-1
* aEF-2

Eukaryotic|

* EEF-1
* EEF1A1
* EEF1A2
* EEF1A3
* EEF1B1
* EEF1B2
* EEF1B3
* EEF1B4
* EEF1D
* EEF1E1
* EEF1G
* EEF2

Release factor|

* Bacterial
* Archaeal
* Eukaryotic (ETF1)

Ribosomal Proteins|

| Cytoplasmic|

| 60S subunit|

* RPL3
* RPL4
* RPL5
* RPL6
* RPL7
* RPL7A
* RPL8
* RPL9
* RPL10
* RPL10A
* RPL10-like
* RPL11
* RPL12
* RPL13
* RPL13A
* RPL14
* RPL15
* RPL17
* RPL18
* RPL18A
* RPL19
* RPL21
* RPL22
* RPL23
* RPL23A
* RPL24
* RPL26
* RPL27
* RPL27A
* RPL28
* RPL29
* RPL30
* RPL31
* RPL32
* RPL34
* RPL35
* RPL35A
* RPL36
* RPL36A
* RPL37
* RPL37A
* RPL38
* RPL39
* RPL40
* RPL41
* RPLP0
* RPLP1
* RPLP2
* RRP15-like
* RSL24D1

|

40S subunit|

* RPSA
* RPS2
* RPS3
* RPS3A
* RPS4 (RPS4X, RPS4Y1, RPS4Y2)
* RPS5
* RPS6
* RPS7
* RPS8
* RPS9
* RPS10
* RPS11
* RPS12
* RPS13
* RPS14
* RPS15
* RPS15A
* RPS16
* RPS17
* RPS18
* RPS19
* RPS20
* RPS21
* RPS23
* RPS24
* RPS25
* RPS26
* RPS27
* RPS27A
* RPS28
* RPS29
* RPS30
* RACK1

Mitochondrial|

| 39S subunit|

* MRPL1
* 2
* 3
* 4
* 5
* 6
* 7
* 8
* 9
* 10
* 11
* 12
* 13
* 14
* 15
* 16
* 17
* 18
* 19
* 20
* 21
* 22
* 23
* 24
* 25
* 26
* 27
* 28
* 29
* 30
* 31
* 32
* 33
* 34
* 35
* 36
* 37
* 38
* 39
* 40
* 41
* 42

|

28S subunit|

* MRPS1
* 2
* 3
* 4
* 5
* 6
* 7
* 8
* 9
* 10
* 11
* 12
* 13
* 14
* 15
* 16
* 17
* 18
* 19
* 20
* 21
* 22
* 23
* 24
* 25
* 26
* 27
* 28
* 29
* 30
* 31
* 32
* 33
* 34
* 35

Other concepts|

* Aminoacyl tRNA synthetase
* Reading frame
* Start codon
* Stop codon
* Shine-Dalgarno sequence/Kozak consensus sequence

* v
* t
* e

Ribosomal RNA / ribosome subunits

Archaea|

* Large:

* Small:

Bacteria (70S)|

* Large:
* 50S
* 5S
* 23S

* Small:
* 30S
* 16S

Eukaryotes (80S)|

| Cytoplasmic|

* Large:
* 60S
* 5S
* 5.8S
* 28S

* Small:
* 40S
* 18S

|

Mitochondrial|

* Large:
* MT-RNR2, 16S

* Small:
* MT-RNR1, 12S

Chloroplast|

* Large chloroplast subunit

* Small chloroplast subunit

*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template