Spatial regulation of EGFR phosphorylation response by protein tyrosine phosphatases

Datum

18.02.2015

Zeit

10:00 - 11:00

Sprecher

Sven Fengler

Zugehörigkeit

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

Sprache

en

Hauptthema

Biologie

Andere Themen

Biologie

Host

Marc Bickle

Beschreibung

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.

Letztmalig verändert: 19.02.2015, 09:43:24