HGNC Approved Gene Symbol: RTKN
Cytogenetic location: 2p13.1 Genomic coordinates (GRCh38): 2:74,425,835-74,441,937 (from NCBI)
The Ras superfamily of small GTPases encompasses a group of ubiquitous regulatory proteins related by both structure and function. Proteins of the Rho subfamily play a pivotal role in the regulation of cytoskeletal organization and the determination of cell polarity. Reid et al. (1996) screened a mouse embryo cDNA library with the yeast 2-hybrid system to identify proteins that interact with Rho. They identified 2.7-kb cDNAs whose open reading frames each encoded a 61-kD, 551-amino acid protein that they named 'rhotekin' after Rho and the Japanese 'teki,' or 'target.' Northern blot analysis of mouse tissues revealed a 3-kb transcript expressed most strongly in brain and kidney, with weaker expression in several other tissues. There was evidence of multiple splicing. The N-terminal Rho-binding region of rhotekin shares 30% identity to that found in 2 other Rho target proteins, rhophilin (601031) and PKN (601032).
By yeast 2-hybrid analysis of a human brain cDNA library, Sudo et al. (2006) found that the C terminus of rhotekin interacted with LIN7B (612331). They confirmed the interaction by protein pull-down assays using recombinant proteins and immunoprecipitation analysis of cotransfected COS-7 cells. A constitutively active version of RHOA (165390), but not activated RAC (602048) or CDC42 (116952), increased the affinity between rhotekin and LIN7B. Lin7 and rhotekin also coimmunoprecipitated from rat brain lysates. Sudo et al. (2006) concluded that LIN7 has a role in neuronal RHO/rhotekin signaling.
Wang et al. (2014) reported that TIP1 (TAX1BP3; 616484) interacted with ARHGEF7 (605477) and RTKN and colocalized with ARHGEF7 at the leading edge of migrating T98G human glioblastoma cells. Knockdown of TIP1 via short hairpin RNA did not change the protein content of ARHGEF7 or RTKN in glioblastoma cell lines, but it caused their intracellular redistribution, changed the appearance of T98G cells toward a highly branched morphology, and inhibited cell migration. Knockdown of TIP1 was accompanied by activation of the Rho GTPases RHOA, CDC42, and RAC1.
Jang et al. (1997) mapped the rhotekin gene to chromosome 6 in mouse. They mapped the human homolog by PCR amplification of a YAC from the corresponding chromosome region 2p13.
Jang, W., Weber, J. S., Harkins, E. B., Meisler, M. H. Localization of the rhotekin gene RTKN on the physical maps of mouse chromosome 6 and human chromosome 2p13 and exclusion as a candidate for mnd2 and LGMD2B. Genomics 40: 506-507, 1997. [PubMed: 9073523] [Full Text: https://doi.org/10.1006/geno.1996.4593]
Reid, T., Furuyashiki, T., Ishizaki, T., Watanabe, G., Watanabe, N., Fujisawa, K., Morii, N., Madaule, P., Narumiya, S. Rhotekin, a new putative target for Rho bearing homology to a serine/threonine kinase, PKN, and rhophilin in the Rho-binding domain. J. Biol. Chem. 271: 13556-13560, 1996. [PubMed: 8662891] [Full Text: https://doi.org/10.1074/jbc.271.23.13556]
Sudo, K., Ito, H., Iwamoto, I., Morishita, R., Asano, T., Nagata, K. Identification of a cell polarity-related protein, Lin-7B, as a binding partner for a Rho effector, rhotekin, and their possible interaction in neurons. Neurosci. Res. 56: 347-355, 2006. [PubMed: 16979770] [Full Text: https://doi.org/10.1016/j.neures.2006.08.003]
Wang, H., Han, M., Whetsell, W., Jr., Wang, J., Rich, J., Hallahan, D., Han, Z. Tax-interacting protein 1 coordinates the spatiotemporal activation of Rho GTPases and regulates the infiltrative growth of human glioblastoma. Oncogene 33: 1558-1569, 2014. [PubMed: 23563176] [Full Text: https://doi.org/10.1038/onc.2013.97]