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Gene Review

SMR3B  -  submaxillary gland androgen regulated...

Homo sapiens

Synonyms: P-B, PBII, PRL3, PROL3, Proline-rich peptide P-B, ...
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Disease relevance of SMR3B

  • Our findings provide direct evidence that PRL-3 may be involved in triggering angiogenesis and establishing microvasculature and it may serve as an attractive therapeutic target with respect to both angiogenesis and cancer metastasis [1].
  • Because PRL-3 mRNA had been reported to be consistently elevated in metastatic samples derived from colorectal cancers, we attempted to investigate if PRL-3 might be involved in tumor angiogenesis and if PRL-3-expressing cells could cross-talk to human umbilical vascular endothelial cells (HUVEC) by using an in vitro coculture system [1].
  • We observed that both PRL-3-expressing Chinese hamster ovary (CHO) cells and PRL-3-expressing DLD-1 human colon cancer cells could redirect the migration of HUVECs toward them; in addition, PRL-3-expressing DLD-1 cells could enhance HUVEC vascular formation [1].
  • Subsequent analysis indicated that the expression of HAI-2/PB suppressed the fibrinolytic activities of both glioblastoma cell lines [2].
  • However, the correlation between the PRL-3 expression and clinical outcome in breast cancer has not been investigated [3].

High impact information on SMR3B

  • PRL-3 Initiates Tumor Angiogenesis by Recruiting Endothelial Cells In vitro and In vivo [1].
  • In vivo injection of PRL-3-expressing CHO cells into nude mice to form local tumors resulted in the recruitment of host endothelial cells into the tumors and initiation of angiogenesis [1].
  • We show here that PRL-3 protein is expressed in fetal heart, developing blood vessels, and pre-erythrocytes but not in their mature counterparts [1].
  • HUVECs were grown with fibroblasts, which were later overlaid with PRL-3-expressing cells [1].
  • Neither PSA, PB, nor ARR3 androgen-responsive reporters could be induced by activation of PKA in the absence of transfected AR [4].

Chemical compound and disease context of SMR3B


Biological context of SMR3B

  • Nucleotide sequence of gene PBII encoding salivary proline-rich protein P-B [8].
  • PBII is 7.1 kb long and contains 3 exons [8].
  • The Pbx binding site in the PRL3 nGRE, located just upstream of the Oct-1 binding site, showed a strong sequence similarity with known Pbx binding sites and bound Pbx with an affinity similar to that of other established Pbx target sequences [9].
  • The GST-WPBF expressed in bacteria binds the Prolamin box (PB) 5'-TGTAAAG-3', derived from the promoter region of a native alpha-gliadin gene encoding a storage protein [10].
  • BACKGROUND: Increasing evidence has suggested that phosphatase of regenerating liver-3 (PRL-3) plays an important role in cancer cell migration, invasion and metastasis [3].

Anatomical context of SMR3B

  • Further investigations will be necessary to establish the origin of statherin and PB salivary peptide in gingival crevicular fluid [11].
  • Transient expression experiments in co-transfected BY-2 protoplast cells demonstrated that WPBF trans-activated transcription from native alpha-gliadin promoter through binding to the intact PB [10].
  • High expression of PRL-3, a protein tyrosine phosphatase, is proved to be associated with lymph node metastasis in gastric carcinoma from previous studies [12].
  • METHODS: MAb against PRL-3 was prepared with the hybridoma technique, and its specificity was confirmed with ELISA and Western blotting assays [6].
  • This part of the sequence is identical to the corresponding region of human P-B cDNA from the submaxillary gland [13].

Associations of SMR3B with chemical compounds

  • Using the SDS-PAGE assay, we found that, in contrast to previous reports, the tyrosine phosphatase PRL-3 may possibly be a dual substrate for both FTase and GGTase-I [14].
  • To determine whether smoking affects androgen and estrogen production and metabolism we measured the MCRs, production rates (PB), androgen and estrogen interconversions, and percent peripheral aromatization in 88 pre- and postmenopausal women grouped as smokers or nonsmokers [15].
  • This anti-invasive effect appeared to be mediated primarily by the inhibitory activity of HAI-2/PB against the serine proteinase-dependent matrix degradation [2].
  • Furthermore, the addition of 4% polyethylene glycol (PEG) gave a better resolution of 4 peaks, resulting in the separation of the overlapped peaks of PB and AB [16].
  • Two biflavonoids, ginkgetin (1) and sciadopitysin (2), were isolated from the MeOH extract of the young branches of Taxus cuspidata, which inhibited phosphatase of regenerating liver-3 (PRL-3) with IC(50) values of 25.8 and 46.2 muM, respectively [17].

Other interactions of SMR3B

  • Detection in human saliva of different statherin and P-B fragments and derivatives [18].
  • Salivary P-B peptide is usually included into the basic proline-rich protein family but it shows some similarities with statherin and its specific biological role is still undefined [18].

Analytical, diagnostic and therapeutic context of SMR3B


  1. PRL-3 Initiates Tumor Angiogenesis by Recruiting Endothelial Cells In vitro and In vivo. Guo, K., Li, J., Wang, H., Osato, M., Tang, J.P., Quah, S.Y., Gan, B.Q., Zeng, Q. Cancer Res. (2006) [Pubmed]
  2. Reduced expression of hepatocyte growth factor activator inhibitor type-2/placental bikunin (HAI-2/PB) in human glioblastomas: implication for anti-invasive role of HAI-2/PB in glioblastoma cells. Hamasuna, R., Kataoka, H., Meng, J.Y., Itoh, H., Moriyama, T., Wakisaka, S., Koono, M. Int. J. Cancer (2001) [Pubmed]
  3. Overexpression of phosphatase of regenerating liver-3 in breast cancer: association with a poor clinical outcome. Wang, L., Peng, L., Dong, B., Kong, L., Meng, L., Yan, L., Xie, Y., Shou, C. Ann. Oncol. (2006) [Pubmed]
  4. Androgen-independent induction of prostate-specific antigen gene expression via cross-talk between the androgen receptor and protein kinase A signal transduction pathways. Sadar, M.D. J. Biol. Chem. (1999) [Pubmed]
  5. Identification and investigation of methylated genes in hepatoma. Chiba, T., Yokosuka, O., Fukai, K., Hirasawa, Y., Tada, M., Mikata, R., Imazeki, F., Taniguchi, H., Iwama, A., Miyazaki, M., Ochiai, T., Saisho, H. Eur. J. Cancer (2005) [Pubmed]
  6. The association of the expression level of protein tyrosine phosphatase PRL-3 protein with liver metastasis and prognosis of patients with colorectal cancer. Peng, L., Ning, J., Meng, L., Shou, C. J. Cancer Res. Clin. Oncol. (2004) [Pubmed]
  7. Lack of effect of human c-Ha-ras proto-oncogene overexpression on prostate carcinogenesis in probasin/SV40 T antigen transgenic rats. Hokaiwado, N., Asamoto, M., Cho, Y.M., Tsuda, H., Shirai, T. Cancer Sci. (2003) [Pubmed]
  8. Nucleotide sequence of gene PBII encoding salivary proline-rich protein P-B. Isemura, S. J. Biochem. (2000) [Pubmed]
  9. Glucocorticoids repress transcription from a negative glucocorticoid response element recognized by two homeodomain-containing proteins, Pbx and Oct-1. Subramaniam, N., Cairns, W., Okret, S. J. Biol. Chem. (1998) [Pubmed]
  10. Wheat Dof transcription factor WPBF interacts with TaQM and activates transcription of an alpha-gliadin gene during wheat seed development. Dong, G., Ni, Z., Yao, Y., Nie, X., Sun, Q. Plant Mol. Biol. (2007) [Pubmed]
  11. Peptides of human gingival crevicular fluid determined by HPLC-ESI-MS. Pisano, E., Cabras, T., Montaldo, C., Piras, V., Inzitari, R., Olmi, C., Castagnola, M., Messana, I. Eur. J. Oral Sci. (2005) [Pubmed]
  12. Inhibition of PRL-3 gene expression in gastric cancer cell line SGC7901 via microRNA suppressed reduces peritoneal metastasis. Li, Z., Zhan, W., Wang, Z., Zhu, B., He, Y., Peng, J., Cai, S., Ma, J. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  13. Tissue distribution and nucleotide sequence of bovine mRNA for salivary proline-rich protein P-B. Isemura, S., Watanabe, S., Fujiwara, S., Sanada, K. Arch. Oral Biol. (2004) [Pubmed]
  14. Identification and specificity profiling of protein prenyltransferase inhibitors using new fluorescent phosphoisoprenoids. Dursina, B., Reents, R., Delon, C., Wu, Y., Kulharia, M., Thutewohl, M., Veligodsky, A., Kalinin, A., Evstifeev, V., Ciobanu, D., Szedlacsek, S.E., Waldmann, H., Goody, R.S., Alexandrov, K. J. Am. Chem. Soc. (2006) [Pubmed]
  15. Androgen and estrogen dynamics in pre- and postmenopausal women: a comparison between smokers and nonsmokers. Longcope, C., Johnston, C.C. J. Clin. Endocrinol. Metab. (1988) [Pubmed]
  16. Application of capillary electrophoresis to the simultaneous determination of betaines in plants. Nishimura, N., Zhang, J., Abo, M., Okubo, A., Yamazaki, S. Analytical sciences : the international journal of the Japan Society for Analytical Chemistry. (2001) [Pubmed]
  17. Biflavonoids inhibited phosphatase of regenerating liver-3 (PRL-3). Choi, S.K., Oh, H.M., Lee, S.K., Jeong, D.G., Ryu, S.E., Son, K.H., Han, D.C., Sung, N.D., Baek, N.I., Kwon, B.M. Nat. Prod. Res. (2006) [Pubmed]
  18. Detection in human saliva of different statherin and P-B fragments and derivatives. Inzitari, R., Cabras, T., Rossetti, D.V., Fanali, C., Vitali, A., Pellegrini, M., Paludetti, G., Manni, A., Giardina, B., Messana, I., Castagnola, M. Proteomics (2006) [Pubmed]
  19. Molecular cloning and sequence analysis of cDNA coding for the precursor of the human salivary proline-rich peptide P-B. Isemura, S., Saitoh, E. J. Biochem. (1994) [Pubmed]
  20. The association of basic proline-rich peptides from human parotid gland secretions with caries experience. Ayad, M., Van Wuyckhuyse, B.C., Minaguchi, K., Raubertas, R.F., Bedi, G.S., Billings, R.J., Bowen, W.H., Tabak, L.A. J. Dent. Res. (2000) [Pubmed]
  21. Expression of PRL-3 phosphatase in human gastric carcinomas: close correlation with invasion and metastasis. Miskad, U.A., Semba, S., Kato, H., Yokozaki, H. Pathobiology (2004) [Pubmed]
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