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Gene Review

RTKN  -  rhotekin

Homo sapiens

Synonyms: B5, RTKN1, Rhotekin
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Disease relevance of RTKN

  • By analyzing the Stanford Microarray Database for the expression profiles of gastric tissues, we also found a progressional increase in RTKN expression in nonneoplastic mucosa, GC, and then lymph node metastases (p < 0.005 by Jonckheere-Terpstra test), suggesting that RTKN expression correlates with GC progression [1].
  • In neuroblastoma Neuro2a cells, Rhotekin and Sept9b were enriched in the tip of neurites, a location where cortical actin reorganization is induced upon stimulation with lysophosphatidic acid [2].
  • Overexpression of rho effector rhotekin confers increased survival in gastric adenocarcinoma [1].
  • While investigating how hypoxia could activate this signaling pathway, using the GST-Rhotekin RBD pulldown assay, we showed the early activation of RhoB by reactive oxygen species under hypoxic conditions and, subsequently, its participation in the ensuing cellular adaptation to hypoxia [3].
  • The C terminus of the B5 receptor for herpes simplex virus contains a functional region important for infection [4].

High impact information on RTKN

  • Repeated vaccination provided significantly higher B5-specific and thus EEV-neutralizing antibody responses [5].
  • Using the Rhotekin binding assay to assess RhoA activation, we observed that engagement of alpha6beta4 by either antibody-mediated clustering or laminin attachment resulted in a two- to threefold increase in RhoA activation, compared with cells maintained in suspension or plated on collagen [6].
  • The center region of Rhotekin was sufficient for the septin reorganization in the cells, and likely to interact indirectly with the C-terminal half of a septin Sept9b, where a GTPase domain is located [2].
  • Reporter gene assays and electrophoretic mobility shift assay confirmed that RTKN overexpression led to constitutive activation of NF-kappaB through the phosphorylation of IkappaB by IKKbeta [7].
  • Conversely, reducing RTKN expression by small interfering RNAs greatly sensitized cells to apoptosis [7].

Biological context of RTKN

  • Compared with BAC clone AC005041 sequence, there were 12 exons for the RTKN gene and it spanned a 16.5-kb genomic region [8].
  • In addition, the RTKN gene was localized to chromosome 2p13 between markers D2S145 at 6.94 cR (LOD > 12) and D2S286 at 8.12 cR (LOD > 9.7) by radiation hybrid panel mapping [8].
  • After the optimal reverse-transcription polymerase chain reaction condition was established, the mRNA expression levels of the RTKN gene in the lesions and tumor-free bladder tissues were examined semiquantitatively, and the relationships between expression levels of RTKN and clinical pathological features were analyzed [9].
  • To explore the mechanisms underlying RTKN-mediated cell survival, a reporter assay was performed [1].
  • The role of RTKN in the pathogenic development of GC was investigated by transfection and expression of RTKN in AGS gastric cells, which express endogenous RTKN at a low basal level [1].

Anatomical context of RTKN

  • In this study, we further showed that RTKN is expressed at a low level in normal cells and is overexpressed in many cancer-derived cell lines [7].
  • Northern analysis using human multiple tissue blots showed that RTKN is predominantly expressed in the kidney and spinal cord, and, to a lesser degree, in the thyroid, tongue, liver, brain, prostate, trachea, and stomach [1].
  • Accordingly, we used the Rhotekin binding assay to assess RhoA activation in intestinal epithelial cells and observed that RhoA was activated by leukotriene D4 (LTD4) [10].
  • Next, we used a rhotekin pulldown assay to confirm directly that IL-1beta deactivates Rho, and further demonstrated that a constitutively active Rho construct rescued astrocytes from developing an IL-1beta-induced reactive phenotype [11].

Associations of RTKN with chemical compounds

  • Consistent with these data, RTKN-expressing cells showed increased chemoresistance to 5-fluorouracil and paclitaxol, and the resistance was greatly attenuated by NF-kappaB inhibitor [7].
  • The RTKN-mediated antiapoptotic effect was blocked by the nuclear factor-kappaB (NF-kappaB) inhibitors, curcumin or parthenolide, but not by the phosphatidylinositol 3'-OH-kinase inhibitor, LY294002, or the MAP kinase inhibitor, PD98059 [7].
  • Our results showed that overexpression of RTKN induced robust activation of NF-kappaB, and RTKN-mediated NF-kappaB activation was suppressed significantly by C3 transferase, an inhibitor of the small GTPase Rho [1].
  • Bovine trachea challenged with a half-maximally effective concentration of carbachol (CCh) was flash-frozen at different times, then assayed for Rho (rhotekin pull-down assay) and ROCK (Western blot; radiometric assay) activities [12].

Regulatory relationships of RTKN


Other interactions of RTKN

  • Similarly, RhoA activity, as measured by the Rhotekin binding assay, was elevated in the PC-3 highly invasive cells [14].
  • The effect of TGF-beta on Rho-GTPase activity was assessed by GST-rhotekin binding domain pulldown assay and detected by Western blot analysis [15].
  • We then demonstrated that Rhotekin and PIST are expressed in developmental stage-specific manners in the rat brain [13].
  • Using pull-down assays with recombinant rhotekin or p21-activated kinase, we demonstrated the activation of RhoGTPases by PMT in DCs [16].

Analytical, diagnostic and therapeutic context of RTKN


  1. Overexpression of rho effector rhotekin confers increased survival in gastric adenocarcinoma. Liu, C.A., Wang, M.J., Chi, C.W., Wu, C.W., Chen, J.Y. J. Biomed. Sci. (2004) [Pubmed]
  2. Possible role of Rho/Rhotekin signaling in mammalian septin organization. Ito, H., Iwamoto, I., Morishita, R., Nozawa, Y., Narumiya, S., Asano, T., Nagata, K. Oncogene (2005) [Pubmed]
  3. Activation of RhoB by hypoxia controls hypoxia-inducible factor-1alpha stabilization through glycogen synthase kinase-3 in U87 glioblastoma cells. Skuli, N., Monferran, S., Delmas, C., Lajoie-Mazenc, I., Favre, G., Toulas, C., Cohen-Jonathan-Moyal, E. Cancer Res. (2006) [Pubmed]
  4. The C terminus of the B5 receptor for herpes simplex virus contains a functional region important for infection. Perez-Romero, P., Fuller, A.O. J. Virol. (2005) [Pubmed]
  5. Quantification of antibody responses against multiple antigens of the two infectious forms of Vaccinia virus provides a benchmark for smallpox vaccination. P??tz, M.M., Midgley, C.M., Law, M., Smith, G.L. Nat. Med. (2006) [Pubmed]
  6. RhoA function in lamellae formation and migration is regulated by the alpha6beta4 integrin and cAMP metabolism. O'Connor, K.L., Nguyen, B.K., Mercurio, A.M. J. Cell Biol. (2000) [Pubmed]
  7. Rho/Rhotekin-mediated NF-kappaB activation confers resistance to apoptosis. Liu, C.A., Wang, M.J., Chi, C.W., Wu, C.W., Chen, J.Y. Oncogene (2004) [Pubmed]
  8. Molecular cloning, expression characterization, and mapping of a novel putative inhibitor of rho GTPase activity, RTKN, to D2S145-D2S286. Fu, Q., Yu, L., Liu, Q., Zhang, J., Zhang, H., Zhao, S. Genomics (2000) [Pubmed]
  9. Association between clinical characteristics and expression abundance of RTKN gene in human bladder carcinoma tissues from Chinese patients. Fan, J., Ma, L.J., Xia, S.J., Yu, L., Fu, Q., Wu, C.Q., Huang, X.H., Jiang, J.M., Tang, X.D. J. Cancer Res. Clin. Oncol. (2005) [Pubmed]
  10. Leukotriene D4 induces association of active RhoA with phospholipase C-gamma1 in intestinal epithelial cells. Thodeti, C.K., Massoumi, R., Bindslev, L., Sjölander, A. Biochem. J. (2002) [Pubmed]
  11. Interleukin-1beta induces a reactive astroglial phenotype via deactivation of the Rho GTPase-Rock axis. John, G.R., Chen, L., Rivieccio, M.A., Melendez-Vasquez, C.V., Hartley, A., Brosnan, C.F. J. Neurosci. (2004) [Pubmed]
  12. Regulation of airway smooth muscle RhoA/ROCK activities by cholinergic and bronchodilator stimuli. Liu, C., Zuo, J., Janssen, L.J. Eur. Respir. J. (2006) [Pubmed]
  13. Possible interaction of a Rho effector, Rhotekin, with a PDZ-protein, PIST, at synapses of hippocampal neurons. Ito, H., Iwamoto, I., Mizutani, K., Morishita, R., Deguchi, T., Nozawa, Y., Asano, T., Nagata, K. Neurosci. Res. (2006) [Pubmed]
  14. Requirement of RhoA activity for increased nuclear factor kappaB activity and PC-3 human prostate cancer cell invasion. Hodge, J.C., Bub, J., Kaul, S., Kajdacsy-Balla, A., Lindholm, P.F. Cancer Res. (2003) [Pubmed]
  15. Contractility as a Prerequisite for TGF-{beta}-Induced Myofibroblast Transdifferentiation in Human Tenon Fibroblasts. Meyer-Ter-Vehn, T., Sieprath, S., Katzenberger, B., Gebhardt, S., Grehn, F., Schlunck, G. Invest. Ophthalmol. Vis. Sci. (2006) [Pubmed]
  16. Pasteurella multocida toxin (PMT) activates RhoGTPases, induces actin polymerization and inhibits migration of human dendritic cells, but does not influence macropinocytosis. Blöcker, D., Berod, L., Fluhr, J.W., Orth, J., Idzko, M., Aktories, K., Norgauer, J. Int. Immunol. (2006) [Pubmed]
  17. The C terminus of YopT is crucial for activity and the N terminus is crucial for substrate binding. Sorg, I., Hoffmann, C., Dumbach, J., Aktories, K., Schmidt, G. Infect. Immun. (2003) [Pubmed]
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