| Description | GNB2L1 encodes a cytosolic protein with a molecular mass of approximatively 35 kDa (317 amino acids). The protein has seven internal Trp-Asp 40 (WD40 domain) repeats. The WD40 repeats of RACK1/GNB2L1 are predicted to form a seven-bladed propeller structure, where each blade is composed of a four-stranded anti-parallel beta-sheet. The highly conserved WD repeat sequence of RACK1/GNB2L1 is found in a number of eukaryotic proteins and is implicated in a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly. |
| Expression | GNB2L1 is ubiquitously expressed in the tissues of higher mammals and humans including brain, liver, and spleen. |
| Localisation | GNB2L1 is a cytosolic protein. |
| Function | GNB2L1 was originally identified as an anchoring protein for protein kinase C beta (PKCbeta), which it stabilises in the active state and anchors to membranes or functional sites. However, evidence has accumulated to support a central role of RACK1/GNB2L1 in critical biological responses. In addition to binding specifically to the active form of PKCbeta isoforms, GNB2L1 also interacts with several other important signaling proteins including the Src kinase family, integrin beta1, integrin beta2, integrin beta3 and integrin beta5, beta-spectrin and dynamin, RasGAP, the androgen receptor , insulin-like growth factor 1 receptor (IGF-1r), Epstein-Barr virus trans-activator protein BZLF1, p73 and pRB.
This suggests that GNB2L1 may act as an anchor or adaptor protein, recruiting other proteins to various transmembrane receptors, providing a platform for protein-protein interactions and acting as the focus for several cell-signaling pathways. Accordingly, a number of cellular functions have been attributed to GNB2L1, e.g. in cell growth, adhesion, protrusion and chemotactic migration.
GNB2L1 might also have an effect on brain function; a reduction in GNB2L1 levels by around 50% has been reported in the brains of aged rats compared with adult or middle aged rat brains. GNB2L1 is also reported to be involved in number of functions in the nervous system. These include neurite growth, dendritic transport, glutamatergic and dopaminergic neurotransmissions and functioning of GABAA receptors.
In addition, up-regulation of GNB2L1 in lymphocytes results in suppression of apoptosis, indicating that it also plays an important role in the regulation of apoptosis. It is also reported that GNB2L1 inhibits the effects of adenovirus E1a on yeast, Saos osteosarcoma and HeLa cells, including the induction of apoptosis.
In addition, GNB2L1 over-expression was reported to protect PC-12 cell survival on withdrawal of Nerve Growth Factor. |
| Homology | GNB2L1 is homologous to the G protein beta subunit, having 42% identity with many conserved amino acid substitutions. |
| Identification of intracellular receptor proteins for activated protein kinase C. |
| Mochly-Rosen D, Khaner H, Lopez J |
| Proceedings of the National Academy of Sciences of the United States of America. 1991 ; 88 (9) : 3997-4000. |
| PMID 1850844 |
| |
| The WD-40 repeat. |
| van der Voorn L, Ploegh HL |
| FEBS letters. 1992 ; 307 (2) : 131-134. |
| PMID 1644165 |
| |
| Cloning of an intracellular receptor for protein kinase C: a homolog of the beta subunit of G proteins. |
| Ron D, Chen CH, Caldwell J, Jamieson L, Orr E, Mochly-Rosen D |
| Proceedings of the National Academy of Sciences of the United States of America. 1994 ; 91 (3) : 839-843. |
| PMID 8302854 |
| |
| Interaction of protein kinase C with RACK1, a receptor for activated C-kinase: a role in beta protein kinase C mediated signal transduction. |
| Mochly-Rosen D, Smith BL, Chen CH, Disatnik MH, Ron D |
| Biochemical Society transactions. 1995 ; 23 (3) : 596-600. |
| PMID 8566424 |
| |
| Functional impairment in protein kinase C by RACK1 (receptor for activated C kinase 1) deficiency in aged rat brain cortex. |
| Pascale A, Fortino I, Govoni S, Trabucchi M, Wetsel WC, Battaini F |
| Journal of neurochemistry. 1996 ; 67 (6) : 2471-2477. |
| PMID 8931480 |
| |
| The role of anchoring protein RACK1 in PKC activation in the ageing rat brain. |
| Battaini F, Pascale A, Paoletti R, Govoni S |
| Trends in neurosciences. 1997 ; 20 (9) : 410-415. |
| PMID 9292970 |
| |
| Rack1, a receptor for activated protein kinase C, interacts with integrin beta subunit. |
| Liliental J, Chang DD |
| The Journal of biological chemistry. 1998 ; 273 (4) : 2379-2383. |
| PMID 9442085 |
| |
| Anchoring proteins for protein kinase C: a means for isozyme selectivity. |
| Mochly-Rosen D, Gordon AS |
| The FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 1998 ; 12 (1) : 35-42. |
| PMID 9438408 |
| |
| The PKC targeting protein RACK1 interacts with the Epstein-Barr virus activator protein BZLF1. |
| Baumann M, Gires O, Kolch W, Mischak H, Zeidler R, Pich D, Hammerschmidt W |
| European journal of biochemistry / FEBS. 2000 ; 267 (12) : 3891-3901. |
| PMID 10849009 |
| |
| RACK1 is up-regulated in angiogenesis and human carcinomas. |
| Berns H, Humar R, Hengerer B, Kiefer FN, Battegay EJ |
| The FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2000 ; 14 (15) : 2549-2558. |
| PMID 11099474 |
| |
| Frequent loss of heterozygosity on chromosome 5 in non-small cell lung carcinoma. |
| Mendes-da-Silva P, Moreira A, Duro-da-Costa J, Matias D, Monteiro C |
| Molecular pathology : MP. 2000 ; 53 (4) : 184-187. |
| PMID 11040940 |
| |
| The WD protein Rack1 mediates protein kinase C and integrin-dependent cell migration. |
| Buensuceso CS, Woodside D, Huff JL, Plopper GE, O'Toole TE |
| Journal of cell science. 2001 ; 114 (Pt 9) : 1691-1698. |
| PMID 11309199 |
| |
| Increased association of brain protein kinase C with the receptor for activated C kinase-1 (RACK1) in bipolar affective disorder. |
| Wang H, Friedman E |
| Biological psychiatry. 2001 ; 50 (5) : 364-370. |
| PMID 11543740 |
| |
| RACK1: a novel substrate for the Src protein-tyrosine kinase. |
| Chang BY, Harte RA, Cartwright CA |
| Oncogene. 2002 ; 21 (50) : 7619-7629. |
| PMID 12400005 |
| |
| Aberrant expression of signaling-related proteins 14-3-3 gamma and RACK1 in fetal Down syndrome brain (trisomy 21). |
| Peyrl A, Weitzdoerfer R, Gulesserian T, Fountoulakis M, Lubec G |
| Electrophoresis. 2002 ; 23 (1) : 152-157. |
| PMID 11824616 |
| |
| Function of p73, not of p53, is inhibited by the physical interaction with RACK1 and its inhibitory effect is counteracted by pRB. |
| Ozaki T, Watanabe K, Nakagawa T, Miyazaki K, Takahashi M, Nakagawara A |
| Oncogene. 2003 ; 22 (21) : 3231-3242. |
| PMID 12761493 |
| |
| The scaffolding protein RACK1 interacts with androgen receptor and promotes cross-talk through a protein kinase C signaling pathway. |
| Rigas AC, Ozanne DM, Neal DE, Robson CN |
| The Journal of biological chemistry. 2003 ; 278 (46) : 46087-46093. |
| PMID 12958311 |
| |
| Functional expression cloning reveals a central role for the receptor for activated protein kinase C 1 (RACK1) in T cell apoptosis. |
| Mourtada-Maarabouni M, Kirkham L, Farzaneh F, Williams GT |
| Journal of leukocyte biology. 2005 ; 78 (2) : 503-514. |
| PMID 15870214 |
| |
| RACK1 has the nerve to act: structure meets function in the nervous system. |
| Sklan EH, Podoly E, Soreq H |
| Progress in neurobiology. 2006 ; 78 (2) : 117-134. |
| PMID 16457939 |
| |
| Identification of specific gene copy number changes in asbestos-related lung cancer. |
| Nymark P, Wikman H, Ruosaari S, Hollmˆ©n J, Vanhala E, Karjalainen A, Anttila S, Knuutila S |
| Cancer research. 2006 ; 66 (11) : 5737-5743. |
| PMID 16740712 |
| |