Regional localization of the hepatocyte growth factor (HGF) gene to human chromosome 7 band q21.1

Fukuyama, Ryuichi; Ichijoh, Yuuka; Minoshima, Shinsei; Kitamura, Naomi; Shimizu, Nobuyoshi

doi:10.1016/0888-7543(91)90149-9

Cited by 40 publications

(10 citation statements)

References 14 publications

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“…HGF belongs to the family of plasminogen-related growth factors (PRGFs) and is also called PRGF-1. Human HGF proteins are transcribed as inactive 90 kDa, single-chain precursors (pro-HGF) from a single gene located on chromosome 7 q 21.1 [9, 10]. Pro-HGF is then converted into an active, mature heterodimeric form, consisting of a disulfide-linked 69 kDa α chain and 34 kDa β chain [11, 12].…”

Section: Hgf/met Tyrosine Kinase Growth Factor Receptor Signaling: Stmentioning

confidence: 99%

Mechanisms of HGF/Met Signaling to Brk and Sam68 in Breast Cancer Progression

et al. 2011

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Signal transduction pathways downstream of receptor tyrosine kinases (RTKs) are often deregulated during oncogenesis, tumor progression, and metastasis. In particular, the peptide growth factor hormone, hepatocyte growth factor (HGF), and its specific receptor, Met tyrosine kinase, regulate cancer cell migration, thereby conferring an aggressive phenotype (Nakamura et al., J Clin Invest 106 (12):1511–1519, 2000; Huh et al., Proc Natl Acad Sci U S A 101:4477–4482, 2004). Additionally, overexpression of Met is associated with enhanced invasiveness of breast cancer cells (Edakuni et al., Pathol Int 51(3):172–178, 2001; Jin et al., Cancer 79(4):749–760, 1997; Tuck et al., Am J Pathol 148(1):225–232, 1996). Here, we review the regulation of recently identified novel downstream mediators of HGF/Met signaling, Breast tumor kinase (Brk/PTK6), and Src-associated substrate during mitosis of 68 kDa (Sam68), and discuss their relevance to mechanisms of breast cancer progression.

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Section: Hgf/met Tyrosine Kinase Growth Factor Receptor Signaling: Stmentioning

confidence: 99%

Mechanisms of HGF/Met Signaling to Brk and Sam68 in Breast Cancer Progression

et al. 2011

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“…The exons encode the α chain, with four kringle structures (highly conserved triple disulfide loop structures), a short spacer region between the α and β chains, and the β chain (Fig. 1A) (4)(5)(6).…”

Section: Introductionmentioning

confidence: 99%

Biological roles of hepatocyte growth factor‑Met signaling from genetically modified animals (Review)

Kato

2017

biom rep

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Abstract. Hepatocyte growth factor (HGF) is produced by stromal and mesenchymal cells, and it stimulates epithelial cell proliferation, motility, morphogenesis and angiogenesis in various organs via tyrosine phosphorylation of its cognate receptor, Met. The HGF-Met signaling pathway contributes in a paracrine manner to the development of epithelial organs, exerts regenerative effects on the epithelium, and promotes the regression of fibrosis in numerous organs. Additionally, the HGF-Met signaling pathway is correlated with the biology of cancer types, neurons and immunity. In vivo analyses using genetic modification have markedly increased the profound understanding of the HGF-Met system in basic biology and its clinical applications. HGF and Met knockout (KO) mice are embryonically lethal. Therefore, amino acids in multifunctional docking sites of Met have been exchanged with specific binding motifs for downstream adaptor molecules in order to investigate the signaling potential of the HGF-Met signaling pathway. Conditional Met KO mice were generated using Cre-loxP methodology and characterization of these mice indicated that the HGF-Met signaling pathway is essential in regeneration, protection, and homeostasis in various tissue types and cells. Furthermore, the results of studies using HGF-overexpressing mice have indicated the therapeutic potential of HGF for various types of disease and injury. In the present review, the phenotypes of Met gene-modified mice are summarized. IntroductionHepatocyte growth factor (HGF). HGF was cloned as a growth factor for hepatocytes (1,2), is identical to scatter factor (SF) and was originally discovered as a fibroblast-derived cell motility factor for epithelial cells (3). HGF is located at 7q21, which spans >70 kb in length and consists of 18 exons. It encodes the inactive pre-pro-HGF, a single chain of 728 amino acids (83 kDa), which includes a signal sequence (1-31), a heavy α chain (69 kDa), and a light β chain (34 kDa). The exons encode the α chain, with four kringle structures (highly conserved triple disulfide loop structures), a short spacer region between the α and β chains, and the β chain (Fig. 1A) (4-6).HGF is produced and secreted by adjacent stromal and mesenchymal cells, it contributes to the development of epithelial organs in a paracrine fashion, exerts regenerative effects on epithelia in the liver, kidney, lung, and other tissues, and promotes the regression of fibrosis in numerous organs (7,8). Various growth factors, cytokines, and prostaglandins upregulate HGF gene expression, including basic fibroblast growth factor, oncostatin M, hypoxia-inducible factor 1α and nuclear factor-κB (NF-κB) (9). By contrast, transforming growth factor (TGF)-β1 was demonstrated to markedly downregulate HGF gene expression (10,11).HGF forms a family with HGF-like protein (HLP), a unique protein with a domain structure similar to that of HGF (12). Macrophage stimulating protein (MSP) was discovered as a serum protein that promoted mouse macrophage motility (13) Abbreviatio...

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“…Metaphase chromosome preparation was made from human diploid B-lymphoblastoid cells GM130B by the standard method (Gill et al, 1985). The karyotype of GMI30B cell line appears normal and FISH was carried out as previously described (Fukuyama et al, 1991 ;Wang et al, 1993) with several modifications. Briefly, human Cot-1 DNA (GIBCO BRL) and the ,~HPO1 clone (containing a 4 kb-fragment of MPZ gene) were labeled with biotin-7-dATP (GIBCO BRL) and digoxigenin-ll-dUTP, respectively.…”

Section: Methodsmentioning

confidence: 99%