Disease relevance of RGS14

• Mild heat stress, but not proteotoxic or transcription-linked stresses, re-localizes the RGS14 from the cytoplasm to promyelocytic leukemia nuclear bodies [1].

High impact information on RGS14

• Its first Ras-binding domain is sufficient to target RGS14 to centrosomes [1].
• Mutation of a nuclear export signal or treatment with leptomycin B causes nuclear accumulation of RGS14 and its association with promyelocytic leukemia protein nuclear bodies [1].
• RGS14 also shuttles between the cytoplasm and nucleus, and its nuclear export depends on the CRM-1 nuclear export receptor [1].
• Expression of RGS14, but not point mutants that disrupt the functional activity of its RGS domain or GoLoco motif, enhances the reporter gene activity [1].
• Here, we describe functional characterization of the GoLoco motif regions of RGS12 and RGS14 [2].

Biological context of RGS14

• Although RGS14 does not act as a GAP for G12/13alpha, it impairs c-fos serum response element activation induced by either a constitutively active mutant of G13alpha (G13alphaQ226L) or by carbachol stimulation of muscarinic type 1 receptors [3].
• RGS14 accelerates GTP hydrolysis by G(ialpha) family members through its RGS domain and suppresses guanine nucleotide dissociation from G(ialpha1) and G(ialpha3) subunits through its C-terminal GoLoco domain [4].
• A search for additional molecules exhibiting an LH domain revealed a limited homology with the catalytic region of a newly identified GTPase-activating protein for heterotrimeric G proteins, RGS14 [5].
• RGS14 shuttles rapidly between the nucleus and cytoplasm, and associates with centrosomes during interphase and mitosis [6].
• RGS14 is a component of the mitotic apparatus that binds directly to and stabilizes microtubules in vitro and is essential for the first cell division in the mouse embryo [7].

Anatomical context of RGS14

• Although RGS14 is constitutively expressed in lymphoid cells, agents that activate B or T lymphocytes further enhance its levels [3].
• RGS14 localizes predominantly in the cytosol, but it can be recruited to membranes by expression of G13alphaQ226L [3].
• Mouse RGS14 encodes a 547-amino-acid protein with an N-terminal RGS domain, which is highly expressed in lymphoid tissues [3].
• However, preincubation of RGS14 with Galpha(i1)-GDP precludes either from promoting microtubule polymerization, suggesting that a functional GTP/GDP cycle is necessary [8].
• Finally, we show that RGS14 is a component of mitotic asters formed in vitro from HeLa cell extracts and that depletion of RGS14 from cell extracts blocks aster formation [8].

Associations of RGS14 with chemical compounds

• We found that RGS14 activity towards heterotrimeric G-proteins, as either a GAP or a GDI (guanine nucleotide dissociation inhibitor), was unaffected by Rap binding [4].

Other interactions of RGS14

• Deletion analysis, as well as in vitro binding experiments, revealed that RGS14 binds Rap proteins through a domain distinct from that carrying the RGS identity, and that this domain shares sequence identity with the Ras/Rap binding domain of B-Raf and Raf-1 kinases [9].
• Our results demonstrate a highly dynamic expression pattern of RGS12 and RGS14 proteins in the central nervous system, and support the view that these proteins may participate not only in G-protein receptor signalling pathways but also in other cellular activities [10].
• When reconstituted with M2 muscarinic receptors (M2) plus either Gi or Go, RGS4 (which has no RBD/GL domain) and full-length RGS14 each markedly stimulates the steady-state GTPase activities of both G proteins, whereas R14-RBD/GL has little or no effect [11].

Analytical, diagnostic and therapeutic context of RGS14

• Regulated transcripts were validated using real-time quantitative RT-PCR, and immunohistochemistry was performed for the most significantly downregulated transcripts in MSA and PD putamen, GPR86 and RGS14, associated with G protein signaling and transcriptional regulation [12].
• Molecular cloning and expression analysis of rat Rgs12 and Rgs14 [13].

References