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Gene Review

RGS14  -  regulator of G-protein signaling 14

Homo sapiens

Synonyms: Regulator of G-protein signaling 14
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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


Biological context of RGS14


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


  1. RGS14 is a centrosomal and nuclear cytoplasmic shuttling protein that traffics to promyelocytic leukemia nuclear bodies following heat shock. Cho, H., Kim, D.U., Kehrl, J.H. J. Biol. Chem. (2005) [Pubmed]
  2. RGS12 and RGS14 GoLoco motifs are G alpha(i) interaction sites with guanine nucleotide dissociation inhibitor Activity. Kimple, R.J., De Vries, L., Tronchère, H., Behe, C.I., Morris, R.A., Gist Farquhar, M., Siderovski, D.P. J. Biol. Chem. (2001) [Pubmed]
  3. RGS14, a GTPase-activating protein for Gialpha, attenuates Gialpha- and G13alpha-mediated signaling pathways. Cho, H., Kozasa, T., Takekoshi, K., De Gunzburg, J., Kehrl, J.H. Mol. Pharmacol. (2000) [Pubmed]
  4. Biochemical characterization of RGS14: RGS14 activity towards G-protein alpha subunits is independent of its binding to Rap2A. Mittal, V., Linder, M.E. Biochem. J. (2006) [Pubmed]
  5. A novel PDZ domain containing guanine nucleotide exchange factor links heterotrimeric G proteins to Rho. Fukuhara, S., Murga, C., Zohar, M., Igishi, T., Gutkind, J.S. J. Biol. Chem. (1999) [Pubmed]
  6. Selective interactions between Gialpha1 and Gialpha3 and the GoLoco/GPR domain of RGS14 influence its dynamic subcellular localization. Shu, F.J., Ramineni, S., Amyot, W., Hepler, J.R. Cell. Signal. (2007) [Pubmed]
  7. Analysis of interactions between regulator of G-protein signaling-14 and microtubules. Martin-McCaffrey, L., Willard, F.S., Pajak, A., Dagnino, L., Siderovski, D.P., D'Souza, S.J. Meth. Enzymol. (2004) [Pubmed]
  8. RGS14 is a microtubule-associated protein. Martin-McCaffrey, L., Willard, F.S., Pajak, A., Dagnino, L., Siderovski, D.P., D'Souza, S.J. Cell Cycle (2005) [Pubmed]
  9. RGS14 is a novel Rap effector that preferentially regulates the GTPase activity of galphao. Traver, S., Bidot, C., Spassky, N., Baltauss, T., De Tand, M.F., Thomas, J.L., Zalc, B., Janoueix-Lerosey, I., Gunzburg, J.D. Biochem. J. (2000) [Pubmed]
  10. Localization of the GoLoco motif carrier regulator of G-protein signalling 12 and 14 proteins in monkey and rat brain. López-Aranda, M.F., Acevedo, M.J., Carballo, F.J., Gutiérrez, A., Khan, Z.U. Eur. J. Neurosci. (2006) [Pubmed]
  11. Novel activity of RGS14 on Goalpha and Gialpha nucleotide binding and hydrolysis distinct from its RGS domain and GDI activity. Hepler, J.R., Cladman, W., Ramineni, S., Hollinger, S., Chidiac, P. Biochemistry (2005) [Pubmed]
  12. Transcriptional changes in multiple system atrophy and Parkinson's disease putamen. Vogt, I.R., Lees, A.J., Evert, B.O., Klockgether, T., Bonin, M., Wüllner, U. Exp. Neurol. (2006) [Pubmed]
  13. Molecular cloning and expression analysis of rat Rgs12 and Rgs14. Snow, B.E., Antonio, L., Suggs, S., Gutstein, H.B., Siderovski, D.P. Biochem. Biophys. Res. Commun. (1997) [Pubmed]
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