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http://krishi.icar.gov.in/jspui/handle/123456789/26683
Title: | A Fyn-specific biosensor reveals localized, pulsatile kinase activity and spatially regulated signaling crosstalk |
Other Titles: | Not Available |
Authors: | Ananya Mukherjee, Randhir Singh, Sreeram Udayan, Sayan Biswas, Purushotham Pothula, Saumya Manmadhan, Geen George, Shilpa Dilip Kumar, Ranabir Das, Balaji M Rao, Akash Gulyani |
ICAR Data Use Licennce: | http://krishi.icar.gov.in/PDF/ICAR_Data_Use_Licence.pdf |
Author's Affiliated institute: | ICAR::Indian Institute of Soil Science |
Published/ Complete Date: | 2019-01-01 |
Project Code: | Not Available |
Keywords: | Not Available |
Publisher: | Cold Spring Harbor Laboratory |
Citation: | Not Available |
Series/Report no.: | Not Available; |
Abstract/Description: | Cell behavior is controlled through spatio-temporally localized protein activity. Despite unique and often contradictory roles played by Src-family-kinases (SFKs) in regulating cell physiology, activity patterns of individual SFKs have remained elusive. Here, we report a biosensor for specifically visualizing active conformation of SFK-Fyn in live cells. We deployed combinatorial library screening to isolate a binding-protein (F29) targeting activated Fyn. Nuclear-magnetic-resonance (NMR) analysis provides the structural basis of F29 specificity for Fyn over homologous SFKs. Using F29, we engineered a sensitive, minimally-perturbing fluorescence-resonance-energy-transfer (FRET) biosensor (FynSensor) that reveals cellular Fyn activity to be spatially localized, pulsatile and sensitive to adhesion/integrin signaling. Strikingly, growth factor stimulation further enhanced Fyn activity in pre-activated intracellular zones. However, inhibition of focal-adhesion-kinase activity not only attenuates Fyn activity, but abolishes growth-factor modulation. FynSensor imaging uncovers spatially-organized, sensitized signaling clusters, direct crosstalk between integrin and growth-factor-signaling, and clarifies how compartmentalized Src-kinase activity may drive cell fate. |
Description: | Not Available |
ISSN: | Not Available |
Type(s) of content: | Research Paper |
Sponsors: | Not Available |
Language: | English |
Name of Journal: | bioRxiv |
Volume No.: | Not Available |
Page Number: | Pages 726133 |
Name of the Division/Regional Station: | Not Available |
Source, DOI or any other URL: | https://doi.org/10.1101/726133 https://scholar.google.com/scholar?oi=bibs&cluster=9567993737596545384&btnI=1&hl=en |
URI: | http://krishi.icar.gov.in/jspui/handle/123456789/26683 |
Appears in Collections: | NRM-IISS-Publication |
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