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ACS Synth Biol. 2014 Nov 21;3(11):788-95. doi: 10.1021/sb5001356. Epub 2014 Jun 13.

Manipulation of endogenous kinase activity in living cells using photoswitchable inhibitory peptides.

Author information

1
Department of Pharmacology and ‡Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina 27599, United States.

Abstract

Optogenetic control of endogenous signaling can be an important tool for probing cell behavior. Using the photoresponse of the LOV2 domain of Avena sativa phototropin 1, we developed analogues of kinase inhibitors whose activity is light dependent. Inhibitory peptides were appended to the Jα helix, where they potently inhibited kinases in the light but were sterically blocked from kinase interaction in the dark. Photoactivatable inhibitors for cyclic-AMP dependent kinase (PKA) and myosin light chain kinase (MLCK) are described, together with studies that shed light on proper positioning of the peptides in the LOV domain. These inhibitors altered endogenous signaling in living cells and produced light-dependent changes in cell morphodynamics.

KEYWORDS:

CREB; MLCK; PKA; membrane dynamics; optogenetics; peptide caging

PMID:
24905630
PMCID:
PMC4277778
DOI:
10.1021/sb5001356
[Indexed for MEDLINE]
Free PMC Article
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