A retraction for this article has been published in Molecular Cancer 2004, 3:1

Short communication

TGFβ₁ activates c-Jun and Erk1 via α_Vβ₆ integrin

Karsta Luettich¹ and Christian Schmidt²

¹  Department of Dermatology, Weill Medical College of Cornell University, 1300 York Avenue, New York, New York, 10021, USA

²  Department of Surgical Oncology and Molecular Oncology, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA

author email corresponding author email

Molecular Cancer 2003, 2:33doi:10.1186/1476-4598-2-33

Published:	23 September 2003

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 α_Vβ₆ integrin is associated with lymph node metastasis of gastric carcinomas. It has been demonstrated that a full TGFβ₁ signal requires both α_Vβ₆ integrin and SMAD pathway. TGFβ₁ binds to α_Vβ₆ via the DLXXL motif, a freely accessible amino acid sequence in the mature form of TGFβ₁. Binding of mature TGFβ₁ to α_Vβ₆ 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.