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Paxillin Signaling | GeneGlobe

Paxillin Signaling


Pathway Description

Cell adhesion to the extracellular matrix (ECM) initiates signals that regulate important physiological events including cell motility and growth, and most often involve changes in the organization of the actin cytoskeleton. Binding of cells to the ECM via integrin receptors leads to a clustering of integrins at the sites of matrix attachment and subsequent recruitment of structural and signaling molecules to these focal contact regions. Proteins present at the cytoplasmic face of focal adhesions (FA) include cytoskeletal proteins such as vinculin and talin. In addition, numerous signaling proteins with enzymatic activity (e.g., kinases and GTPases) are also components of FA. The clustering of these structural and signaling components results in cytoskeletal changes required for changes in cell morphology and physiology. Paxillin plays an important role in transducing signals from integrin receptors to the actin cytoskeleton.Paxillin is a multidomain, focal contact adapter that localizes with integrin-β1, FAK, vinculin and certain kinases at FA. It links integrin signaling with p38 MAPK and JNK pathways. It is phosphorylated following cell activation by ECM, growth factors, angiotensin-II and neuropeptides during embryogenesis, metastasis and wound repair. The NH2 terminus of paxillin contains five leucine-rich domains termed LD motifs which mediate protein-protein interactions. Its primary function is as a molecular adapter or scaffold protein, providing multiple docking sites at the plasma membrane for an array of signaling proteins such as kinases and structural proteins. Phosphorylation of residues in the N-terminus of paxillin by these kinases permits the regulated recruitment of downstream effector molecules such as Crk, which is important for cell motility and modulation of gene expression by the various MAPK cascades.

The recruitment of signaling and structural proteins to paxillin results in cytoskeletal changes required for regulation of cell motility in such events as embryonic development, wound repair and tumor metastasis. Several of the paxillin-binding proteins have oncogenic equivalents such as v-Src, v-Crk and BCR-ABL, which use paxillin both as a substrate and as a docking site to perturb, and even bypass, the normal adhesion and growth factor signaling cascades necessary for controlled cell proliferation.