Genetic ablation of zyxin causes Mena/VASP mislocalization, increased motility, and deficits in actin remodeling.

Focal adhesions are specialized regions of the cell surface where integrin receptors and associated proteins link the extracellular matrix to the actin cytoskeleton. To define the cellular role of the focal adhesion protein zyxin, we characterized the phenotype of fibroblasts in which the zyxin gene was deleted by homologous recombination. Zyxin-null fibroblasts display enhanced integrin-dependent adhesion and are more migratory than wild-type fibroblasts, displaying reduced dependence on extracellular matrix cues.

TGF-beta inhibitors for the treatment of cancer.

Advances in understanding the role of transforming growth factor (TGF)-beta in tumorigenesis have led to the development of TGF-beta inhibitors for cancer treatment. Three platforms of TGF-beta inhibitors have evolved: antisense oligonucleotides, monoclonal antibodies and small molecules. In this review, the current stage of development of each known TGF-beta inhibitor will be discussed.

DU145 human prostate carcinoma invasiveness is modulated by urokinase receptor (uPAR) downstream of epidermal growth factor receptor (EGFR) signaling.

Tumor cell motility and invasion have been linked to upregulated signaling from both the epidermal growth factor receptor (EGFR) and that for urokinase-type plasminogen activator (uPAR). However, we do not know whether these events are interdependent or unrelated, despite the obvious diagnostic and therapeutic implications. Gene microarray analyses have suggested that EGFR signaling via phospholipase C-gamma (PLCgamma) induces uPAR transcription.

The Kindler syndrome protein is regulated by transforming growth factor-beta and involved in integrin-mediated adhesion.

Transforming growth factor-beta1 (TGF-beta1) contributes to tumor invasion and cancer progression by increasing the motility of tumor cells. To identify genes involved in TGF-beta-mediated cell migration, the transcriptional profiles of human mammary epithelial cells (HMEC) treated with TGF-beta were compared with untreated cells by cDNA microarray analysis. One gene up-regulated by TGF-beta was recently named kindlerin (Jobard, F.

Parallel purification of three catalytic subunits of the protein serine/threonine phosphatase 2A family (PP2A(C), PP4(C), and PP6(C)) and analysis of the interaction of PP2A(C) with alpha4 protein.

The protein serine/threonine phosphatase (PP) type 2A family consists of three members: PP2A, PP4, and PP6. Specific rabbit and sheep antibodies corresponding to each catalytic subunit, as well as a rabbit antibody recognizing all three subunits, were utilized to examine the expression of these enzymes in select rat tissue extracts. PP2A, PP4, and PP6 catalytic subunits (PP2A(C), PP4(C), and PP6(C), respectively) were detected in all rat tissue extracts examined and exhibited some differences in their levels of expression.

Members of the Zyxin family of LIM proteins interact with members of the p130Cas family of signal transducers.

Integrin binding to extracellular matrix proteins induces formation of signaling complexes at focal adhesions. Zyxin co-localizes with integrins at sites of cell-substratum adhesion and is postulated to serve as a docking site for the assembly of multimeric protein complexes involved in regulating cell motility. Recently, we identified a new member of the zyxin family called TRIP6.