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Molecular Cancer
Published in: Molecular Cancer 1/2003

Open Access 01-12-2003 | Short communication

TGFβ1 activates c-Jun and Erk1 via αVβ6 integrin

Authors: Karsta Luettich, Christian Schmidt

Published in: Molecular Cancer | Issue 1/2003

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Abstract

Transforming growth factor β (TGFβ) plays an important role in animal development and many cellular processes. A variety of cellular functions that are required for tumor metastasis are controlled by integrins, a family of cell adhesion receptors. Overexpression of αVβ6 integrin is associated with lymph node metastasis of gastric carcinomas. It has been demonstrated that a full TGFβ1 signal requires both αVβ6 integrin and SMAD pathway. TGFβ1 binds to αVβ6 via the DLXXL motif, a freely accessible amino acid sequence in the mature form of TGFβ1. Binding of mature TGFβ1 to αVβ6 leads to immobilization and tyrosine phosphorylation of proteins, which are associated with focal adhesions, a hallmark of integrin-mediated signal transduction. Here, we show that binding of mature TGFβ1 recruits the mitogen-activated protein kinase kinase kinase 1 (MEKK1), a mediator of c-Jun activation, and the extracellular signaling-regulated kinase-1 (Erk1) to focal adhesions. In addition, the p21-activated kinase 1 (PAK1) is associated with focal adhesions and differentially phosphorylated upon TGFβ1 stimulation. We conclude that TGFβ1 activates c-Jun via the MEKK1/p38 MAP kinase pathway and influences cytoskeletal organization. These finding may provide a link between TGFβ1 and the metastatic behavior of cancers.
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Metadata
Title
TGFβ1 activates c-Jun and Erk1 via αVβ6 integrin
Authors
Karsta Luettich
Christian Schmidt
Publication date
01-12-2003
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2003
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/1476-4598-2-33

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