Analysis of substrate recognition and regulatory mechanisms for protein kinases.
| Project/Area Number |
17K07383
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Cell biology
|
|---|
| Research Institution | Nagoya University |
|---|
Principal Investigator |
Amano Mutsuki 名古屋大学, 医学系研究科, 准教授 (90304170)
|
|---|
| Project Period (FY) |
2017-04-01 – 2021-03-31
|
| Project Status |
Completed (Fiscal Year 2020)
|
| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
|
|---|
| Keywords | リン酸化 / プロテインキナーゼ / 細胞内シグナル伝達 / 基質 / 細胞内情報伝達 / シグナル伝達 / キナーゼ / プロテオーム |
|---|
| Outline of Final Research Achievements |
In this study, we analyzed substrate recognition and regulatory mechanisms of protein kinases, as well as physiological and pathological functions. We identified the specific sequences of MYPT1, a substrate for Rho-kinase, as docking motifs (DMs) conferring selectivity and efficiency of phosphorylation by Rho-kinase. We also found that longer intrinsically disordered regions (IDRs) are preferably phosphorylated by stochastic simulation model using our screening dataset for 15 protein kinases. In addition, functional analyses revealed that MAPK-Npas4/MKL2 (mouse striatal neurons) and PKN-MKL1 (mouse heart) signals are involved in dopamine-induced gene expression and stress-induced cardiac dysfunction, respectively.
|
| Academic Significance and Societal Importance of the Research Achievements |
タンパク質リン酸化は細胞内シグナル伝達に中心的な役割を果たし、生理機能のみならず種々の疾患に深く関わっている。本研究では、独自に開発したキナーゼ基質スクリーニング法（KISS法）より得られたデータを基に、リン酸化シグナルを理解するための分子基盤（キナーゼの基質認識機構）、および種々のキナーゼー基質シグナルの疾患への関わりについて理解を深めることができた。
|
Report
(5 results)
Research Products
(20 results)
-
-
-
-
-
[Journal Article] Protein Kinase N Promotes Stress-Induced Cardiac Dysfunction Through Phosphorylation of Myocardin-Related Transcription Factor A and Disruption of Its Interaction With Actin.2019
Author(s)
Sakaguchi T, Takefuji M, Wettschureck N, Hamaguchi T, Amano M, Kato K, Tsuda T, Eguchi S, Ishihama S, Mori Y, Yura Y, Yoshida T, Unno K, Okumura T, Ishii H, Shimizu Y, Bando YK, Ohashi K, Ouchi N, Enomoto A, Offermanns S, Kaibuchi K, Murohara T.
-
Journal Title
Circulation.
Volume: 140
Issue: 21
Pages: 1737-1752
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
-
-
-
[Journal Article] Balance between dopamine and adenosine signals regulates the PKA/Rap1 pathway in striatal medium spiny neurons2018
Author(s)
Zhang XJ, Nagai T, Ahammad RU, Kuroda K, Nakamuta S, Nakano T, Yukinawa N, Funahashi Y, Yamahashi Y, Amano M, Yoshimoto J, Yamada K, and Kaibuchi K.
-
Journal Title
Neurochemistry International
Volume: 122
Pages: 8-18
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
-
-
-
-
-
-
-
-
-
-
