| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2006: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2005: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Research Abstract |
In some of growth factor receptors, which involve tyrosine kinases in their molecule, it is well known that these receptors dimerize each other and ligand-induced stimulation is transduced into the cells with these dimerized receptors. Recent researches clarified that G-protein-coupled receptors, another type of the cell surface receptors also form their dimerized receptors, function as a dimer and those will regulate the intracellular signaling mechanisms.
We have researched the signal transduction mechanisms of endothelin by using rabbit heart tissue, and found that the ligand selectivity of endothelin receptors in rabbit heart is different from those reported by another species. We examined whether there are differences in molecular structure of endothelin receptors in rabbit and in other species, but the differences of the amino acid sequences of these receptors are little. Then we next examined the possibilities that endothelin receptors in rabbit heart function as dimer, and dimerized receptors-induced change in signaling mechanisms are responsible for the atypical responses for endothelin in rabbit heart tissue. There are two types of endothelin receptors named ETA and ETB, and we found both ETA and ETB receptors dimerized each other. Furthermore, it was found that these endothein receptors might form trimer, not only dimer. However, a clear result, which showed the change in intracellular mechanisms that might be induced by dimerized (or oligomerized) receptor, could not be obtained. Further analyses have been carried out to clarify the physiological and pharmacological roles of multimerized receptor in modulating the cell function.
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