| 1.Research Institution | Japanese Foundation for Cancer Research (JFCR) | |
| 2.Research Area | Life Science | |
| 3.Research Field | Cellular Signaling | |
| 4.Term of Project | FY1996〜FY2000 | |
| 5.Project Number | 96L00304 | |
| 6.Title of Project | Study on the Signal Transduction by Serine-Threonine Kinase Receptors |
| Name | Institution,Department | Title of Position |
| Kohei Miyazono | JFCR Cancer Inst., Biochemistry | Chief |
8.Core Members
| Names | Institution,Department | Title of Position |
| Masahiro Kawabata | JFCR Cancer Inst., Biochemistry | Ass. Member |
| Takeshi Imamura | JFCR Cancer Inst., Biochemistry | Ass. Member |
| Tetsuo Noda | JFCR Cancer Inst., Cell Biology | Chief |
9.Cooperating Researchers
| Names | Institution,Department | Title of Position |
| Mitsuyasu Kato | JFCR Cancer Inst., Biochemistry | Ass. Member |
| Makiko Fujii | JFCR Cancer Inst., Biochemistry | Post-doc |
| Hideyuki Beppu | JFCR Cancer Inst., Biochemistry | Post-doc |
10.Summary of Research Results
|
We studied the signaling mechanisms of serine-threonine kinase receptors, which are the receptors for members of transforming growth factor-β (TGF-β) superfamily. We studied: 1) signaling mechanisms of serine-threonine kinase receptors in invertebrates, e.g. Drosophila, 2) signaling mechanisms of serine-threonine kinase receptors in mammalian cells, and 3) studies on signaling by serine-threonine kinase receptors using gene targeting in mice. We first isolated Smad6, an inhibitory Smads in mammals, and proposed that Smads can be classified into three subtypes, i.e. receptor-regulated Smads, common-partner Smads, and inhibitory Smads. We demonstrated several proteins interacting Smads, including Runx and Ski. We also showed biological activities of Smads, e.g. their effects on bone and cartilage formation, using adenoviral vector systems. In Drosophila melanogaster, we reported severla proteins involved in erine-threonine kinase receptor signaling. These include DIAP1, Dad, Medea, dSmad2, and Schnurri. We further prepared mice lacking Smad2 and BMP type II receptor. The BMP type II receptor is responsible for the pathogenesis of human primary pulmonary hypertension. We were able to show some biochemical evidence that the mutations of the BMP type II receptor block signaling activity of BMPs. |
11.Key Words
(1)TGF-β、(2)BMP、(3)serine-threonine kinase
(4)receptor、(5)Smad、(6)Drosophila
(7)adenovirus vector、(8)gene targeting、(9)signal transduction
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