Cortactin, an 80/85-kilodalton pp60src substrate, is a filamentous actin-binding protein enriched in the cell cortex.

Abstract

Abstract. Two relatexl cellular proteins, p80 and p85 (cortactin), become phosphorylated on tyrosine in pp60"~-transformed cells and in cells stimulated with certain growth factors. The amino-terminal half of cortactin is comprised of multiple copies of an internal, tandem 37-amino acid repeat. The carboxylterminal half contains a distal SH3 domain. We report that cortactin is an F-actin-binding protein. The binding to F-actin is specific and saturable. The aminoterminal repeat region appears to be both necessary and sufficient to mediate actin binding, whereas the SH3 domain had no apparent effect on the actinbinding activity. Cortactin, present in several different cell types, is enriched in cortical structures such as membrane ruffles and lamellipodia. The properties of cortactin indicate that it may be important for microfilament-membrane interactions as well as transducing signals from the cell surface to the cytoskeleton. We suggest the name cortactin, reflecting the cortical subcellular localization and its actin-binding activity.

Overexpression of EMS1/cortactin in NIH3T3 fibroblasts causes increased cell motility and invasion in vitro

“…These are areas in the cell where cytoskeletal reorganizations are believed to occur prerequisite to cell migration over and degradation of extracellular matrices (Chen, 1989). Furthermore, cortactin's domain structure consists of several tandem repeats in the amino terminus which have been shown to bind to actin, at least in vitro (Wu and Parsons, 1993). Other domains of cortactin consist of proline, serine and threonine rich regions, as well as a carboxy terminal SH3 domain.…”

“…Previous studies have demonstrated that cortactin has a submembraneous localization in the cell cortex, including cell leading edges, membrane ru es and ®lopodia (Wu and Parsons, 1993). We therefore performed immuno¯uorescence using monoclonal cortactin antibody 4F11 to determine the subcellular localization of the cortactin protein expressed in the cortactin overexpressing clonal cell lines.…”

The SH3 Domain of Amphiphysin Binds the Proline-rich Domain of Dynamin at a Single Site That Defines a New SH3 Binding Consensus Sequence

“…Dynamin I contains a proline-rich COOH-terminal region of about 100 amino acids that interacts in vitro and in vivo with a variety of SH3 domain-containing proteins, including PLC-␥, the p85 subunit of phosphatidylinositol 3-kinase, Src, Grb2, and amphiphysin (15,16,19,23,37). The multiplicity of the binding partners for this domain revealed by in vitro and in vivo studies may be explained by either a promiscuous interaction of various SH3 domains with several proline-rich stretches or by the presence in the tail of dynamin I of an array of distinct sites, each of which specifically binds certain SH3 domains.…”

An invasion-related complex of cortactin, paxillin and PKCμ associates with invadopodia at sites of extracellular matrix degradation

“…Cortactin binds to F-actin in vitro, colocalizes with cortical actin at ru ing membranes, and possesses actin-bundling activity that is modulated by c-Src, suggesting a role in membrane motility (Wu and Parsons, 1993;Huang et al, 1997). In v-Srcactivated ®broblasts transformed by Rous sarcoma virus, cell motility and invasiveness are increased, cortactin becomes phosphorylated on tyrosine residues enabling an association with v-Src in podosomes (Okamura and Resh, 1995).…”