Hepatocyte growth factor rapidly induces the tyrosine phosphorylation of 41-kDa and 43-kDa proteins in mouse keratinocytes

Chatani, Yuji; Itoh, Akio; Tanaka, Eiko; Hattori, Akira; Nakamura, Toshikazu; Kohno, Michiaki

doi:10.1016/0006-291x(92)91706-v

Cited by 22 publications

(7 citation statements)

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“…Other studies also suggest relationship between MAPK activation and keratinocyte proliferation. In mouse keratinocytes (PAM-212) cells, HGF and EGF, which are potent mitogens for these cells, both stimulate the DNA synthesis and the tyrosine phosphorylation of 41-kDa and 43-kDa proteins (MAPK) (38). MAPK cascade plays an important role in carcinogenic development.…”

Section: Mitogen-activated Protein Kinase Cascadementioning

confidence: 99%

“…There are few publications about the MAPK signal transduction pathway in keratinocytes and its role is not fully understood. In keratinocytes MAPKs can be activated by EGF (37-39), UV light (40), hepatocyte growth factor (HGF) (38), IL-4 (41), the skin tumor promoter butylated hydroxytoluene hydroperoxide (BHTOOH) (42) and probably by TPA (37,43). However, this activation may be mediated by different ways and the physiological significance seems to be bilateral (Fig.…”

Section: Mitogen-activated Protein Kinase Cascadementioning

confidence: 99%

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Signal transduction in keratinocytes

Mitev

Miteva

1999

Experimental Dermatology

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Signal transduction in keratinocytesand their proliferation and differentiation are stimulated by a variety of biological factors. The major mechanism by which cells (keratinocytes) respond to extracellular signals, is changing in protein phosphorylation. Key words: keratinocytes -proliferation -The protein phosphorylation is a consequence of the ligand/receptor binddifferentiation -protein kinases -STAT ing which leads to activation of several transduction systems. In this review we emphasize on different signal transduction pathways in kera-

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Section: Mitogen-activated Protein Kinase Cascadementioning

confidence: 99%

Section: Mitogen-activated Protein Kinase Cascadementioning

confidence: 99%

Signal transduction in keratinocytes

Mitev

Miteva

1999

Experimental Dermatology

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“…The EGF receptor also has tyrosine kinase activity, and its autophosphorylated tyrosine residues are associated with signaling molecules such as phospholipase C␥, Shc, and Gab1 (32)(33)(34)(35)(36). Although receptors for both HGF/SF and EGF seem to be able to activate common signaling pathways, such as PI3-K and Ras-mitogen-activated protein (MAP) kinase pathways (37)(38)(39)(40)(41)(42), the set of pathways activated in response to HGF/SF or EGF depends on the individual systems used for experiments.…”

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confidence: 99%

Suppression of Adriamycin-induced Apoptosis by Sustained Activation of the Phosphatidylinositol-3′-OH kinase-Akt Pathway

Takeuchi

Ito

2004

Journal of Biological Chemistry

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The mechanisms by which growth factors trigger signal transduction pathways leading to protection against apoptosis are of great interest. In this study, we investigated the effect of hepatocyte growth factor (HGF/SF) and epidermal growth factor (EGF) on adriamycin ( Cell-surface biotin-labeling analysis showed that the HGF/SF receptor remained on the cell surface until at least 30 min after HGF/SF addition but that the EGF receptor level on the cell surface was attenuated at an earlier time after EGF addition. These results indicate that HGF/SF, but not EGF, transmitted protective signals against ADR-induced apoptosis by causing sustained activation of the PI3-K-Akt signaling pathway. Furthermore, the difference in antiapoptotic capacity between HGF/SF and EGF is explained, at least in part, by the delayed down-regulation of the HGF/SF receptor.

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“…It belongs to the cell surface receptor tyrosine kinase family (49), and all the activities of HGF are mediated through the cytoplasmic domain of the c-Met receptor (15,32,55,68). Like other growth factors, HGF induces the tyrosine phosphorylation of several intracellular proteins (5,19,46,53). It is shown that tyrosine phosphorylation of some of these molecules, such as phosphatidylinositol 3Ј-kinase, phospholipase C-␥, growth factor receptorbinding protein 2 (GRB-2), and c-Src, or their association with the autophosphorylated c-Met receptor is required for signal transduction of some cellular responses (53, 72).…”

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confidence: 99%

Growth Factor-Induced Tyrosine Phosphorylation of Hrs, a Novel 115-Kilodalton Protein with a Structurally Conserved Putative Zinc Finger Domain

Komada

Kitamura

1995

Molecular and Cellular Biology

154

158

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The activation of growth factor receptor tyrosine kinases leads to tyrosine phosphorylation of many intracellular proteins which are thought to play crucial roles in growth factor signaling pathways. We previously showed that tyrosine phosphorylation of a 115-kDa protein is rapidly induced in cells treated with hepatocyte growth factor. To clarify the structure and possible function of the 115-kDa protein (designated Hrs for hepatocyte growth factor-regulated tyrosine kinase substrate), we purified this protein from B16-F1 mouse melanoma cells by anti-phosphotyrosine immunoaffinity chromatography and determined its partial amino acid sequences. On the basis of the amino acid sequences, we molecularly cloned the cDNA for mouse Hrs. The nucleotide sequence of the cDNA revealed that Hrs is a novel 775-amino-acid protein with a putative zinc finger domain that is structurally conserved in several other proteins. This protein also contained a proline-rich region and a proline-and glutamine-rich region. The expression of Hrs mRNA was detected in all adult mouse tissues tested and also in embryos. To analyze the Hrs cDNA product, we prepared a polyclonal antibody against bacterially expressed Hrs. Using this antibody, we showed by subcellular fractionation that Hrs is localized to the cytoplasm; we also showed that that tyrosine phosphorylation of Hrs is induced in cells treated with epidermal growth factor or platelet-derived growth factor. These results suggest that Hrs plays a unique and important role in the signaling pathway of growth factors.Peptide growth factors exert pleiotropic biological effects on a variety of cell types (9). These effects include mitogenesis, enhanced motility, differentiation, metabolism, and morphogenesis. Signals for all these effects are mediated through specific receptors expressed on the cell surface. Growth factor receptors possess intrinsic tyrosine kinase activity in the cytoplasmic domains, and the binding of growth factors to the receptors enhances the kinase activity, leading to tyrosine phosphorylation of many intracellular proteins in addition to the receptors themselves (65, 70). Many of these tyrosine kinase substrates, such as phospholipase C-␥ (37, 39), ras 27), the p85 regulatory subunit of phosphatidylinositol 3Ј-kinase (7,26,66), Shc (52), Nck (36,48), and Src family tyrosine kinases (8, 42), possess Src homology 2 (SH2) domains and bind tightly to the phosphotyrosinecontaining sequences in the autophosphorylated receptors through their SH2 domains (4, 31). On the other hand, proteins that do not have an SH2 domain are also tyrosine phosphorylated in growth factor-stimulated cells. They include cRaf serine/threonine kinase (43), mitogen-activated protein kinase (56), insulin receptor substrate-1 (64), and several proteins identified by the use of anti-phosphotyrosine antibody affinity chromatography, such as the Src substrate p120 (24), eps8 (11), and eps15 (12). Thus, the growth factor signaling pathways are considered to involve the tyrosine phosphorylation of both S...

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Hepatocyte growth factor rapidly induces the tyrosine phosphorylation of 41-kDa and 43-kDa proteins in mouse keratinocytes

Cited by 22 publications

References 19 publications

Signal transduction in keratinocytes

Signal transduction in keratinocytes

Suppression of Adriamycin-induced Apoptosis by Sustained Activation of the Phosphatidylinositol-3′-OH kinase-Akt Pathway

Growth Factor-Induced Tyrosine Phosphorylation of Hrs, a Novel 115-Kilodalton Protein with a Structurally Conserved Putative Zinc Finger Domain

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