Visualizing the mechanical activation of Src
By Yingxiao Wang, E. Botvinick, Yihua Zhao, M. Berns, S. Usami, Roger Tsien, Shu Chien. Nature, 2005
697 citations recorded by the source corpus.
The mechanical environment crucially influences many cell functions. However, it remains largely mysterious how mechanical stimuli are transmitted into biochemical signals. Src is known to regulate the integrin–cytoskeleton interaction, which is essential for the transduction of mechanical stimuli. Using fluorescent resonance energy transfer (FRET), here we develop a genetically encoded Src reporter that enables the imaging and quantification of spatio-temporal activation of Src in live cells. We introduced a local mechanical stimulation to human umbilical vein endothelial cells (HUVECs) by applying laser-tweezer traction on fibronectin-coated beads adhering to the cells. Using the Src reporter, we observed a rapid distal Src activation and a slower directional wave propagation of Src activation along the plasma membrane. This wave propagated away from the stimulation site with a speed (mean ± s.e.m.) of 18.1 ± 1.7 nm s-1. This force-induced directional and long-range activation of Src was abolished by the disruption of actin filaments or microtubules. Our reporter has thus made it possible to monitor mechanotransduction in live cells with spatio-temporal characterization. We find that the transmission of mechanically induced Src activation is a dynamic process that directs signals via the cytoskeleton to spatial destinations.
Subfields: Atomic and Molecular Physics, and Optics, Biophysics, Cell Biology
View Paper: https://www.semanticscholar.org/paper/aea2191456ec02f3d616be26fffa117086ac29a7
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Citations in the corpus
- Effects of Disturbed Flow on Vascular Endothelium: Pathophysiological Basis and Clinical Perspectives (2011, background): “The association of Shc with integrins requires VE-cadherin, and the activation of Shc requires VEGFR-2 and Src, a tyrosine kinase that localizes to EC junctions in response to mechanical force (350, 602).”
- The myofibroblast: paradigm for a mechanically active cell. (2010, background): “, 2006), Src (Wang et al., 2005), and p130CAS (Sawada et al.”
- TNFα Shedding in Mechanically Stressed Cardiomyocytes is Mediated by Src Activation of TACE (2015, background): “As a protein tyrosine kinase, Src is well-established as a key molecule that mediates mechanotransdution in various types of load-sensitive cells [Torsoni et al., 2003; Wang et al., 2005; Rangaswami et al., 2010; Niu et al., 2013].”
- Balancing forces: architectural control of mechanotransduction (2011, neutral): “The ECM in force homeostasis and disease Mechanotransduction occurs on very fast timescales that can exceed the speed of signalling through soluble factors by orders of magnitud”
- Force sensing by mechanical extension of the Src family kinase substrate p130Cas. (2006, background): “Possible Mechanisms for Stretch-Increased Cas Phosphorylation Although Src was shown to be mechanically activated using genetically engineered reporters (Wang et al., 2005), it is not clear how endogenous c-Src is activated or if it is indirectly activated by force.”