| 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. |
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| Functional expression cloning reveals a central role for the receptor for activated protein kinase C 1 (RACK1) in T cell apoptosis. |
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| Function of p73, not of p53, is inhibited by the physical interaction with RACK1 and its inhibitory effect is counteracted by pRB. |
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| Functional impairment in protein kinase C by RACK1 (receptor for activated C kinase 1) deficiency in aged rat brain cortex. |
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| PMID 8931480 |
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| Aberrant expression of signaling-related proteins 14-3-3 gamma and RACK1 in fetal Down syndrome brain (trisomy 21). |
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| PMID 11824616 |
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| The scaffolding protein RACK1 interacts with androgen receptor and promotes cross-talk through a protein kinase C signaling pathway. |
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| PMID 12958311 |
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| Cloning of an intracellular receptor for protein kinase C: a homolog of the beta subunit of G proteins. |
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| Increased association of brain protein kinase C with the receptor for activated C kinase-1 (RACK1) in bipolar affective disorder. |
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| PMID 11543740 |
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| The WD-40 repeat. |
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| PMID 1644165 |
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