Alternative titles; symbols
HGNC Approved Gene Symbol: MST1
Cytogenetic location: 3p21.31 Genomic coordinates (GRCh38): 3:49,683,947-49,689,474 (from NCBI)
Han et al. (1991) isolated an MST1 cDNA from a human liver cDNA library. The deduced protein contains 4 kringle domains followed by a serine protease domain. Because this domain structure was identical to that found in hepatic growth factor (HGF; 142409), Han et al. (1991) proposed that the protein be called HGF-like (HGFL). The 2 proteins share about 50% sequence identity.
Han et al. (1991) determined that the HGFL gene contains 18 exons and spans approximately 47 kb.
Han et al. (1991) identified the HGFL gene at the DNF15S2 locus on human chromosome 3 (3p21). The gene for acylpeptide hydrolase (APH; 102645) was located 444 bp downstream of the HGFL gene, but on the complementary strand. The DNF15S2 locus had been proposed to code for one or more tumor suppressor genes since this locus is deleted in DNA from small cell lung carcinoma, renal cell carcinoma, and von Hippel-Lindau syndrome.
Degen et al. (1992) demonstrated that the mouse Hgfl gene is on chromosome 9, distal to the transferrin locus. The region surrounding the Hgfl locus shows homology of synteny to 3p21. Yoshimura et al. (1993) assigned the human gene for macrophage stimulating protein to chromosome 3. They also found that a cDNA identified a unique sequence on chromosome 1, suggesting the location there of a member of the same gene family.
Sakamoto et al. (1997) showed that the RON tyrosine kinase (600168), the receptor for MSP, is expressed on the ciliated epithelia of the mucociliary transport apparatus of the lung. Furthermore, they showed that MSP stimulated ciliary motility in these cells by activating RON.
For discussion of an association between variation in the MST1 gene and inflammatory bowel disease, see IBD12 (612241).
For discussion of an association between variation in the MST1 gene and primary sclerosis cholangitis, see PSC (613806).
To assess the in vivo effects of total loss of HGFL, Bezerra et al. (1998) generated mice with targeted disruption of the gene resulting in loss of the protein. Embryogenesis proceeded normally and followed a mendelian pattern of genetic transmission. Mice homozygous for the targeted allele, Hgfl -/- mice, were fertile and grew to adulthood without obvious phenotypic abnormalities in unchallenged animals, except for development of lipid-containing cytoplasmic vacuoles in hepatocytes throughout the liver lobules. The histologic changes were not accompanied by discernible changes in synthetic or excretory hepatic functions. Hematopoiesis appeared unaltered, and although macrophage activation was delayed in the absence of Hgfl, migration to the peritoneal cavity upon challenge with thioglycollate was similar in null and in wildtype mice. Challenged with incision to skin, null mice displayed normal wound healing. These data demonstrated that HGFL is not essential for embryogenesis, fertility, or wound healing. The mice will provide a valuable means to assess the role of HGFL in hepatic and systemic responses to inflammatory and infectious stimuli in vivo.
Bezerra, J. A., Carrick, T. L., Degen, J. L., Witte, D., Degen, S. J. F. Biological effects of targeted inactivation of hepatocyte growth factor-like protein in mice. J. Clin. Invest. 101: 1175-1183, 1998. [PubMed: 9486989] [Full Text: https://doi.org/10.1172/JCI1744]
Degen, S. J. F., Gilbert, D. J., Jenkins, N. A., Copeland, N. G. Assignment of the gene coding for hepatocyte growth factor-like protein to mouse chromosome 9. Genomics 13: 1368-1369, 1992. [PubMed: 1354648] [Full Text: https://doi.org/10.1016/0888-7543(92)90073-2]
Han, S., Stuart, L. A., Degen, S. J. F. Characterization of the DNF15S2 locus on human chromosome 3: identification of a gene coding for four kringle domains with homology to hepatocyte growth factor. Biochemistry 30: 9768-9780, 1991. [PubMed: 1655021] [Full Text: https://doi.org/10.1021/bi00104a029]
Sakamoto, O., Iwama, A., Amitani, R., Takehara, T., Yamaguchi, N., Yamamoto, T., Masuyama, K., Yamanaka, T., Ando, M., Suda, T. Role of macrophage-stimulating protein and its receptor, RON tyrosine kinase, in ciliary motility. J. Clin. Invest. 99: 701-709, 1997. [PubMed: 9045873] [Full Text: https://doi.org/10.1172/JCI119214]
Yoshimura, T., Yuhki, N., Wang, M.-H., Skeel, A., Leonard, E. J. Cloning, sequencing, and expression of human macrophage stimulating protein (MSP, MST1) confirms MSP as a member of the family of kringle proteins and locates the MSP gene on chromosome 3. J. Biol. Chem. 268: 15461-15468, 1993. [PubMed: 8393443]