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Gene Review

RPSA  -  ribosomal protein SA

Homo sapiens

Synonyms: 37 kDa laminin receptor precursor, 37/67 kDa laminin receptor, 37LRP, 40S ribosomal protein SA, 67 kDa laminin receptor, ...
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Disease relevance of RPSA


High impact information on RPSA

  • Indeed, mutant LAMR1 caused specific changes to gene expression in cardiomyocytes, as detected by gene chip analysis [6].
  • Furthermore, because selectivity was not observed in vitro or in transient transactivation experiments, these findings suggest that an understanding of the selectivity mechanism may require an analysis of the endogenous p40 locus [7].
  • p37 and p40 are two cloned gene products of the five-subunit human cellular DNA replication factor activator 1 (A1) protein complex (also called replication factor C) [8].
  • The 67-kDa laminin receptor (67LR) is a nonintegrin cell-surface receptor with high affinity for laminin, which plays a key role in tumor invasion and metastasis [9].
  • In vitro G-CSF treatment, alone or combined with exposure to marrow-derived endothelial cells, induced 67LR up-regulation in marrow HSCs; moreover, anti-67LR antibodies significantly inhibited transendothelial migration of G-CSF-stimulated marrow HSCs [9].

Chemical compound and disease context of RPSA

  • As angiogenesis in the pathological setting of proliferative retinopathy is a major cause of blindness in the Western world we examined the expression of 67LR in a murine model of hyperoxia-induced retinopathy that exhibits retinal neovascularization [10].
  • Adeno-associated virus (AAV) vectors readily express the gene for geneticin-resistance under control of the AAV p40 promoter when chromosomally integrated at low copy number in mammalian cells [11].
  • In the present work we investigate the effects of progestins and estrogen on the expression of 67LR in two sublines of the T47D human breast cancer cells: weakly tumorigenic, poorly invasive parental T47D cells and a highly tumorigenic, more invasive T47Dco subclone [12].

Biological context of RPSA


Anatomical context of RPSA

  • Immunolabeling of the original tissue with antibodies against these two genes confirmed overexpression, validating our strategy: 67LR was not expressed in the normal urothelium but was present in the tumor, whereas TATI expression was confined to umbrella cells in the normal urothelium, but extended to all cell layers in the tumor [15].
  • The 67 kD laminin receptor (67LR) binds laminin-1 (LN), major component of the basement membrane, with high affinity [3].
  • CD38(bright+) plasma cells in fresh multiple myeloma (MM) bone marrow (BM) samples showed weaker 67LR expression, but expression increased after direct exposure to a BM endothelial cell line (4LHBMEC) [3].
  • The authors explored the potential biologic significance of expression of 67LR in 148 patients with axillary lymph node negative breast carcinoma [5].
  • We investigated the role of 67LR in granulocyte colony-stimulating factor (G-CSF)-induced mobilization of CD34(+) hematopoietic stem cells (HSCs) from 35 healthy donors [9].

Associations of RPSA with chemical compounds

  • METHODS: Formalin fixed, paraffin embedded histologic sections were immunohistochemically evaluated for 67LR using monoclonal antibody MLuC5 [5].
  • Upon incubation of the most highly purified fractions with Mn-ATP or Mg-ATP, p40 was the only protein phosphorylated on tyrosine [16].
  • 32P-labeled p40 immunoprecipitated from extracts of metabolically labeled cells by affinity-purified anti-p40 antibodies contained both phosphoserine and phosphotyrosine [16].
  • In the presence of a synthetic peptide (peptide G) corresponding to the 67LR laminin binding site, the rate of laminin-1 degradation by the cysteine proteinase cathepsin B was significantly increased, and a new proteolytic fragment particularly active in in vitro cell migration assays was generated [17].
  • Moreover, cytokine treatment resulted in down-modulated expression of the alpha6 integrin subunit and the 67LR [18].

Other interactions of RPSA

  • TATI was more consistently overexpressed than 67LR in all tumor grades and stages [15].
  • We observed an increased promoter activity in wt p53 cells as compared to the mutated-p53 line when the first intron of the 37LRP gene was present in the reporter construct [14].
  • Nevertheless, in the subgroup of 67LR positive patients, positivity for estrogen receptor was associated with significantly longer overall survival (P = 0.008) [5].

Analytical, diagnostic and therapeutic context of RPSA

  • Immunofluorescence microscopy and ligand overlay assays showed that 67LR is present on the HBMEC membrane and interacts with CNF1 protein as well as the CDPGYIGSR laminin peptide [1].
  • Sequence analysis revealed that the MGr1-Ag and 37LRP genes shared the same coding sequence [2].
  • We have previously shown that 67LR detection in PC tissues from radical prostatectomy (RP) specimens is an independent predictor of biochemical (PSA) relapse in patients with clinically localized PC [19].
  • This retrospective study was designed to investigate the relationship between overexpression of the 67 kD laminin receptor (67LR) using immunohistochemistry, and several clinicopathological parameters including overall survival in human gastric adenocarcinoma [4].
  • Although the overexpression of the 67LR tended to correlate with lower survival rates, the correlation was not statistically significant due to the limited sample size [4].


  1. 67-kDa laminin receptor promotes internalization of cytotoxic necrotizing factor 1-expressing Escherichia coli K1 into human brain microvascular endothelial cells. Kim, K.J., Chung, J.W., Kim, K.S. J. Biol. Chem. (2005) [Pubmed]
  2. Multidrug-resistance-associated protein MGr1-Ag is identical to the human 37-kDa laminin receptor precursor. Shi, Y., Zhai, H., Wang, X., Wu, H., Ning, X., Han, Y., Zhang, D., Xiao, B., Wu, K., Fan, D. Cell. Mol. Life Sci. (2002) [Pubmed]
  3. Laminin-1-induced migration of multiple myeloma cells involves the high-affinity 67 kD laminin receptor. Vande Broek, I., Vanderkerken, K., De Greef, C., Asosingh, K., Straetmans, N., Van Camp, B., Van Riet, I. Br. J. Cancer (2001) [Pubmed]
  4. Overexpression of the 67 kD laminin receptor correlates with the progression of gastric carcinoma. Lee, W.A., Kim, W.H., Kim, Y.I., Yang, H.K., Kim, J.P., Kleinman, H.K. Pathol. Res. Pract. (1996) [Pubmed]
  5. Laminin receptor in lymph node negative breast carcinoma. Nadji, M., Nassiri, M., Fresno, M., Terzian, E., Morales, A.R. Cancer (1999) [Pubmed]
  6. Lamr1 functional retroposon causes right ventricular dysplasia in mice. Asano, Y., Takashima, S., Asakura, M., Shintani, Y., Liao, Y., Minamino, T., Asanuma, H., Sanada, S., Kim, J., Ogai, A., Fukushima, T., Oikawa, Y., Okazaki, Y., Kaneda, Y., Sato, M., Miyazaki, J., Kitamura, S., Tomoike, H., Kitakaze, M., Hori, M. Nat. Genet. (2004) [Pubmed]
  7. Selective requirement for c-Rel during IL-12 P40 gene induction in macrophages. Sanjabi, S., Hoffmann, A., Liou, H.C., Baltimore, D., Smale, S.T. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  8. The subunits of activator 1 (replication factor C) carry out multiple functions essential for proliferating-cell nuclear antigen-dependent DNA synthesis. Pan, Z.Q., Chen, M., Hurwitz, J. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  9. The metastasis-associated 67-kDa laminin receptor is involved in G-CSF-induced hematopoietic stem cell mobilization. Selleri, C., Ragno, P., Ricci, P., Visconte, V., Scarpato, N., Carriero, M.V., Rotoli, B., Rossi, G., Montuori, N. Blood (2006) [Pubmed]
  10. The 67-kd laminin receptor is preferentially expressed by proliferating retinal vessels in a murine model of ischemic retinopathy. Stitt, A.W., McKenna, D., Simpson, D.A., Gardiner, T.A., Harriott, P., Archer, D.B., Nelson, J. Am. J. Pathol. (1998) [Pubmed]
  11. Effect of a viral rep gene on transformation of cells by an adeno-associated virus vector. Mendelson, E., Smith, M.G., Miller, I.L., Carter, B.J. Virology (1988) [Pubmed]
  12. Expression of 67 kDa laminin receptor in human breast cancer cells: regulation by progestins. Shi, Y.E., Torri, J., Yieh, L., Sobel, M.E., Yamada, Y., Lippman, M.E., Dickson, R.B., Thompson, E.W. Clin. Exp. Metastasis (1993) [Pubmed]
  13. Isolation from a multigene family of the active human gene of the metastasis-associated multifunctional protein 37LRP/p40 at chromosome 3p21.3. Jackers, P., Minoletti, F., Belotti, D., Clausse, N., Sozzi, G., Sobel, M.E., Castronovo, V. Oncogene (1996) [Pubmed]
  14. p53-dependent downregulation of metastasis-associated laminin receptor. Modugno, M., Tagliabue, E., Ardini, E., Berno, V., Galmozzi, E., De Bortoli, M., Castronovo, V., Ménard, S. Oncogene (2002) [Pubmed]
  15. Identification of genes up-regulated in urothelial tumors: the 67-kd laminin receptor and tumor-associated trypsin inhibitor. Diggle, C.P., Cruickshank, S., Olsburgh, J.D., Pellegrin, S., Smith, B., Banks, R.E., Selby, P.J., Knowles, M.A., Southgate, J., Harnden, P. Am. J. Pathol. (2003) [Pubmed]
  16. Novel yeast protein kinase (YPK1 gene product) is a 40-kilodalton phosphotyrosyl protein associated with protein-tyrosine kinase activity. Dailey, D., Schieven, G.L., Lim, M.Y., Marquardt, H., Gilmore, T., Thorner, J., Martin, G.S. Mol. Cell. Biol. (1990) [Pubmed]
  17. Identification of a novel function for 67-kDa laminin receptor: increase in laminin degradation rate and release of motility fragments. Ardini, E., Sporchia, B., Pollegioni, L., Modugno, M., Ghirelli, C., Castiglioni, F., Tagliabue, E., Ménard, S. Cancer Res. (2002) [Pubmed]
  18. Co-regulation and physical association of the 67-kDa monomeric laminin receptor and the alpha6beta4 integrin. Ardini, E., Tagliabue, E., Magnifico, A., Butò, S., Castronovo, V., Colnaghi, M.I., Ménard, S. J. Biol. Chem. (1997) [Pubmed]
  19. Detection of the 67-kD laminin receptor in prostate cancer biopsies as a predictor of recurrence after radical prostatectomy. Waltregny, D., de Leval, L., Coppens, L., Youssef, E., de Leval, J., Castronovo, V. Eur. Urol. (2001) [Pubmed]
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