| Co-Investigator(Kenkyū-buntansha) |
TOKUMITSU Hiroshi Nagoya University, Pharmacology, Associate Professor, 医学部, 助手 (20237077)
WATANABE Masato Nagoya University, Pharmacology, Associate Professor, 医学部, 助手 (30220924)
HAGIWARA Masatoshi Nagoya University, Pharmacology, Associate Professor, 医学部, 助手 (10208423)
KOBAYASHI Ryoji Nagoya University, Pharmacology, Assistant Professor, 医学部, 助教授 (00020917)
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| Research Abstract |
Protein kinases are enzymes which tansfer Pi into some proteins. These reactions have been revealed to be involved in the regulation of many cellular function. now that the number of protein kinases has reached to over 100, it is essential to study them with structural and functional approach to clarify the physiological function of each protein kinase. The aim of our study is, (1) to presume the tertiary structure of the functional domain of protein kinase, (2) to develop the new specific protein kinase inhibitors, and (3), it is final aim, to clarify the physiological function of protein kinases. Using specific inhibitor for Ca2+/calmodulin dependent protein kinase II(CaM kinase II), KN-62, we succeeded in revealing the involvement of CaM kinase II in smooth muscle contraction, the central regulation of systemic pressure, secretion of insulin or endotherin and so on. H-89, specific inhibitor for cAMP dependent protein kinase(A-kinase), revealed the involvement of the A-kinase in the regulation of transcription of c-fos gene, and in the regulation of induction of immediately early genes. We succeeded in synthesizing the novel specific inhibitor for CaM kinase II or for the novel protein kinase activated by MAP kinase, which is a key molecule for regulating the signals induced by various extracellular stimuli. KN-62 was revealed to inhibit CaM kinase V which was a novel Ca2+/calmodulin dependent protein kinase with respect with calmodulin. On the basis of this result, it will be suggested that the calmodulin binding domain of CaM kinase II is quite similar to that of CaM kinase V.
Taken together, we succeeded in clarifying the function of protein kinases, in developing the new specific inhibitors, and in clearing the similarity between the tertiary structure of calmodulin binding domain of CaM kinase II and CaM kinase V.
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