Identification of a conserved residue responsible for the autoinhibition of cGMP‐dependent protein kinase Iα and β

FEBS Letters

Michibata, Hideo²  Yuasa, Keizo²  Omori, Kenji²  Yanaka, Noriyuki¹ 

[1] Discovery Research Laboratory, Tanabe Seiyaku Co. Ltd., 16-89 Kashima 3-chome, Yodogawa-ku, Osaka 532-8505, Japan;Discovery Research Laboratory, Tanabe Seiyaku Co. Ltd., 2-50, Kawagishi 2-chome, Toda, Saitama 335-8505, Japan

关键词: cGK;    cGMP-dependent protein kinase;    cAK;    cAMP-dependent protein kinase;    cTnI;    cardiac troponin I;   

DOI  :  10.1016/S0014-5793(99)01786-X

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

We isolated a constitutively active form of cGMP-dependent protein kinase Iα (cGK Iα) by PCR-driven random mutagenesis. The replacement of Ile-63 by Thr in the autoinhibitory domain results in the enhancement of autophosphorylation and the basal kinase activity in the absence of cGMP. The hydrophobicity at position 63 is essential for the inactive state of cGK Iα, and Ile-78 of cGK Iβ is also required for the autoinhibitory property. Furthermore, cGK Iα (Ile-63-Thr) is constitutively active in vivo. These findings suggest that a conserved residue in the autoinhibitory domain was involved in the autoinhibition of both cGK Is.

【 授权许可】

Unknown