한빛사 논문
Sangwon Shin,#[a] Jisu Choe,#[a] Youngchan Park,#[a],[b] Donghyun Jeong,[a] Hyunjoon Song,[b] Youngmin You,* [c] Daeha Seo,* [a] and Jaeheung Cho* [a]
[a] Department of Emerging Materials Science, DGIST Daegu 42988, Republic of Korea
[b] Department of Chemistry, KAIST Daejeon 34141, Republic of Korea.
[c] Division of Chemical Engineering and Materials Science, Ewha Womans University. Seoul 03760, Republic of Korea.
[#] These authors contributed equally to this work
*To whom correspondence should be addressed.
Abstract
Cells use gaseous molecules such as nitric oxide (NO) to transmit both of intracellular and intercellular signals. In principle, the endogenous small molecules regulate physiological changes, but it is unclear how randomly diffusive molecules trigger and discriminate signaling programs. Here, we show that gasotransmitters use time‐dependent dynamics to discriminate the endogenous and exogenous inputs. For a real‐time stimulation of cell signaling, we synthesized a photo‐cleavable metal‐nitrosyl complex, [CoIII(MDAP)(NO)(CH3CN)]2+ (MDAP = N,N’‐dimethyl‐2,11‐diaza[3,3](2,6)pyridinophane), which can stably deliver and selectively release NO with fine temporal resolution in the cytosolic region. We demonstrate its utility by investigating the extracellular signal–regulated kinases (ERKs). By measuring the dynamics of ERK responses using a kinase translocation reporter (KTR), we revealed how the cells use both exogenous and endogenous NO to disentangle cellular responses. This technique can be used not only to understand how diverse cellular signaling networks are interconnected dynamically but also to control drug delivery system.
Keywords : nitric oxide, Signal transduction, Photolysis, Cobalt(III)-nitrosyl complex, Kinase translocation reporter (KTR)
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