Cortactin in the Test Tube

stress fibers, do not contain cortactin. Despite the substantial size of the cortactin literature (currently the word “cortactin” appears in 339 articles), the most fundamental questions are still open. Thus, although cortactin has been implicated in the above-mentioned processes, its exact role is still not clearly defined. Its obvious participation in many of these fundamental events together with the elusiveness of its exact role render cortactin the gray eminence of the cytoskeleton. Moreover, the role of tyrosine (and serine/threonine) phosphorylation in the regulation of its function, localization, and interaction with other proteins is also far from being fully understood. Thus both the regulation of cortactin and the regulation by cortactin remain a challenge of cytoskeletal biology. Furthermore, cortactin has established itself as a medically important protein, since it is not only overexpressed in a variety of human cancers but appears to play a causative role in tumor cell migration and metastasis (58, 74). In the past few years, cortactin was the focus of several excellent reviews (19, 62, 85, 103). In this short overview, we would like to approach the topic from a physiological point of view, or, more precisely, we attempt to provide a “topical physiology” of cortactin by summarizing the various loci where cortactin acts and the associated cell biological processes in which it appears to participate. We have to start, however, with a more detailed look at its biochemistry and genetics.