Sli2 (Ypk1), a Homologue of Mammalian Protein Kinase SGK, Is a Downstream Kinase in the Sphingolipid-Mediated Signaling Pathway of Yeast
| Autor: | Daisuke Tanoue, Hiromu Takematsu, Yasunori Kozutsumi, Kazutoshi Mori, Yidi Sun, Tetsuro Fujita, Toshisuke Kawasaki, Ritsuko Taniguchi, Toshiyuki Yamaji |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Ceramide
Saccharomyces cerevisiae Proteins Sphingosine kinase Saccharomyces cerevisiae Protein Serine-Threonine Kinases Biology Immediate-Early Proteins Fatty Acids Monounsaturated Fungal Proteins Glycogen Synthase Kinase 3 chemistry.chemical_compound Cell Growth and Development Molecular Biology Cyclin-dependent kinase 1 Sphingosine Serine C-palmitoyltransferase Nuclear Proteins Cell Biology Protein-Tyrosine Kinases Sphingolipid Cell biology chemistry Biochemistry lipids (amino acids peptides and proteins) Signal transduction Sphingomyelin Immunosuppressive Agents Signal Transduction |
| Zdroj: | Molecular and Cellular Biology. 20:4411-4419 |
| ISSN: | 1098-5549 |
| DOI: | 10.1128/mcb.20.12.4411-4419.2000 |
| Popis: | Recent reports have shown that sphingolipids are involved in several biological functions, including adhesion, differentiation, growth, and apoptosis (3, 22, 23, 25, 26, 44, 58). Ceramide and sphingosine-1-phosphate, which are metabolic products of sphingolipids, are thought to be upregulated by several stimuli and to serve as second messengers in signal transduction pathways (24, 27, 50, 55). Sphingosine-1-phosphate is upregulated by the platelet-derived growth factor stimulus (51), and the increase in sphingosine-1-phosphate promotes the growth of 3T3 fibroblast cells (66). Recently, G-protein-coupled cell surface receptors for sphingosine-1-phosphate were found in several cell lines (4, 40, 68). Furthermore, the possible involvement of intracellular sphingosine-1-phosphate in several signal transduction pathways has been postulated (31, 59). In addition to sphingosine-1-phosphate, intracellular ceramide upregulation through the sphingomyelin cycle on stimulation by tumor necrosis factor alpha (56), Fas ligand (11, 20, 21), or UV or γ irradiation (24) causes apoptosis of Jurkat T cells and several other cell lines, although exogenously added ceramide does not exert all of the downstream effects of these stimulants (30, 57, 64). The yeast Saccharomyces cerevisiae synthesizes sphingolipids similarly to mammalian sphingolipids except that phytosphingosine rather than sphingosine is the predominant sphingoid base (Fig. (Fig.1),1), and it lacks cell surface receptors for sphingosine-1-phosphate (16). Therefore, yeast is a useful system for studying the intracellular sphingolipid-mediated signaling pathway. Indeed, yeast has a sphingosine kinase which produces sphingosine-1-phosphate from sphingosine, and the former is a crucial substance involved in the respiration of yeast cells (39). Ceramide has been shown to induce G1 arrest in yeast via a ceramide-activated protein phosphatase (49). A new phosphatase, which modulates stress responses through sphingolipid metabolites, has also been isolated from yeast (42). However, most of the downstream pathway of intracellular sphingolipid-mediated signaling has not been well clarified in yeast or mammals. FIG. 1 Major sphingolipid biosynthetic pathways in yeast and mammalian cells. ISP-1 was isolated from Isaria sinclairii as a new type of potent immunosuppressant, the structure of which is homologous to that of sphingosine (17). In our previous studies, ISP-1 was found to inhibit mammalian serine palmitoyltransferase (SPT), which catalyzes the first step of sphingolipid biosynthesis. ISP-1 induced the apoptosis of mouse cytotoxic T cells (17, 45, 48) and rat Purkinje cells (18), which was triggered by reduction of the intercellular pools of sphingolipid metabolites. These results suggest that ISP-1 is a useful tool for the depletion of intracellular sphingolipids and for studying the sphingolipid-mediated signaling pathway in both mammals and yeast. We report that ISP-1 prevents yeast proliferation due to the inhibition of sphingolipid biosynthesis and that a multicopy suppressor gene of ISP-1 encodes a downstream kinase of the sphingolipid-mediated signaling pathway in yeast. |
| Databáze: | OpenAIRE |
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