Spatial regulation of EGFR phosphorylation response by protein tyrosine phosphatases

Date

Feb 18, 2015

Time

10:00 AM - 11:00 AM

Speaker

Sven Fengler

Affiliation

MPI of Molecular Physiology, Department of Systemic Cell Biology, Dortmund, Germany

Language

en

Main Topic

Biologie

Other Topics

Biologie

Host

Marc Bickle

Description

The intrinsic epidermal growth factor receptor (EGFR) kinase activity opposed by tyrosine phosphatases (PTPs) determines its phosphorylation state and thereby its signaling capacity after epidermal growth factor stimuli. After EGF binding, the majority of EGFR is internalized and encounters PTPs at different cellular locations, but how these interactions generates a finite response to growth factors is unclear. We used cell-arrays in combination with fluorescent lifetime imaging microscopy (CA-FLIM) to quantify the phosphorylation of EGFR with spatial resolution in breast cancer derived MCF7 cells transfected with different siRNAs or plasmid-cDNAs to perturb PTP expression. We identified more than 20 PTPs that clearly regulated EGFR phosphorylation. Classification of the temporal phosphorylation profiles of EGFR resulted in 5 functional groups of PTPs that affect early, late or the overall EGFR phosphorylation profile. PTP localization thereby dictates when it interacts with EGFR. This spatially exerted control of PTPs on EGFR activity thereby shapes the finite response to growth factors.

Last modified: Feb 19, 2015, 9:43:24 AM