EGF regulates tyrosine phosphorylation and membrane-translocation of the scaffold protein Tks5.
BACKGROUND
Tks5/FISH is a scaffold protein comprising of five SH3 domains and one PX domain. Tks5 is a substrate of the tyrosine kinase Src and is required for the organization of podosomes/invadopodia implicated in invasion of tumor cells. Recent data have suggested that a close homologue of Tks5, Tks4, is implicated in the EGF signaling.


RESULTS
Here, we report that Tks5 is a component of the EGF signaling pathway. In EGF-treated cells, Tks5 is tyrosine phosphorylated within minutes and the level of phosphorylation is sustained for at least 2 hours. Using specific kinase inhibitors, we demonstrate that tyrosine phosphorylation of Tks5 is catalyzed by Src tyrosine kinase. We show that treatment of cells with EGF results in plasma membrane translocation of Tks5. In addition, treatment of cells with LY294002, an inhibitor of PI 3-kinase, or mutation of the PX domain reduces tyrosine phosphorylation and membrane translocation of Tks5.


CONCLUSIONS
Our results identify Tks5 as a novel component of the EGF signaling pathway.
Institute of Enzymology, Research Center for Natural Sciences, Hungarian Academy of Sciences, Budapest 1113, Hungary.
Anna
A
Fekete
Department of Medical Chemistry, Semmelweis University Medical School, Budapest 1094, Hungary.
Gábor
G
Bőgel
Department of Medical Chemistry, Semmelweis University Medical School, Budapest 1094, Hungary.
Szabolcs
S
Pesti
Department of Physiology, Semmelweis University Medical School, Budapest, Hungary.
Zalán
Z
Péterfi
Department of Physiology, Semmelweis University Medical School, Budapest, Hungary ; "Lendület" Peroxidase Enzyme Research Group of the Semmelweis University and the Hungarian Academy of Sciences, Budapest 1094, Hungary.
Miklós
M
Geiszt
Institute of Enzymology, Research Center for Natural Sciences, Hungarian Academy of Sciences, Budapest 1113, Hungary ; Department of Medical Chemistry, Semmelweis University Medical School, Budapest 1094, Hungary.
László
L
Buday
EGF receptor; PI 3-kinase; PX domain; Src; Tks4; Tks5