Cover Image

Phenotypic profiling of the human genome reveals gene products involved in plasma membrane targeting of SRC kinases

SRC proteins are non-receptor tyrosine kinases that play key roles in regulating signal transduction by a diverse set of cell surface receptors. They contain N-terminal SH4 domains that are modified by fatty acylation and are functioning as membrane anchors. Acylated SH4 domains are both necessary a...

Full description

Saved in:
Bibliographic Details
Main Authors: Ritzerfeld, Julia (Author) , Remmele, Steffen (Author) , Wang, Tao (Author) , Temmerman, Koen (Author) , Brügger, Britta (Author) , Wegehingel, Sabine (Author) , Tournaviti, Stella (Author) , Strating, Jeroen R. P. M. (Author) , Wieland, Felix T. (Author) , Neumann, Beate (Author) , Ellenberg, Jan (Author) , Lawerenz, Christian (Author) , Hesser, Jürgen (Author) , Erfle, Holger (Author) , Pepperkok, Rainer (Author) , Nickel, Walter (Author)
Format: Article (Journal)
Language:English
Published: July 27, 2011
In: Genome research
Year: 2011, Volume: 21, Issue: 11, Pages: 1955-1968
ISSN:1549-5469
DOI:10.1101/gr.116087.110
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1101/gr.116087.110
Verlag, lizenzpflichtig, Volltext: https://genome.cshlp.org/content/21/11/1955
Get full text
Author Notes:Julia Ritzerfeld, Steffen Remmele, Tao Wang, Koen Temmerman, Britta Brügger, Sabine Wegehingel, Stella Tournaviti, Jeroen R.P.M. Strating, Felix T. Wieland, Beate Neumann, Jan Ellenberg, Chris Lawerenz, Jürgen Hesser, Holger Erfle, Rainer Pepperkok, and Walter Nickel
Description
Summary:SRC proteins are non-receptor tyrosine kinases that play key roles in regulating signal transduction by a diverse set of cell surface receptors. They contain N-terminal SH4 domains that are modified by fatty acylation and are functioning as membrane anchors. Acylated SH4 domains are both necessary and sufficient to mediate specific targeting of SRC kinases to the inner leaflet of plasma membranes. Intracellular transport of SRC kinases to the plasma membrane depends on microdomains into which SRC kinases partition upon palmitoylation. In the present study, we established a live-cell imaging screening system to identify gene products involved in plasma membrane targeting of SRC kinases. Based on siRNA arrays and a human model cell line expressing two kinds of SH4 reporter molecules, we conducted a genome-wide analysis of SH4-dependent protein targeting using an automated microscopy platform. We identified and validated 54 gene products whose down-regulation causes intracellular retention of SH4 reporter molecules. To detect and quantify this phenotype, we developed a software-based image analysis tool. Among the identified gene products, we found factors involved in lipid metabolism, intracellular transport, and cellular signaling processes. Furthermore, we identified proteins that are either associated with SRC kinases or are related to various known functions of SRC kinases such as other kinases and phosphatases potentially involved in SRC-mediated signal transduction. Finally, we identified gene products whose function is less defined or entirely unknown. Our findings provide a major resource for future studies unraveling the molecular mechanisms that underlie proper targeting of SRC kinases to the inner leaflet of plasma membranes.
Item Description:Gesehen am 16.09.2022
Physical Description:Online Resource
ISSN:1549-5469
DOI:10.1101/gr.116087.110

Similar Items