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In this study, we have determined that CD44v10 and Rho\u2010Kinase (ROK) are physically associated as a complex in vivo. Using a recombinant fragment of ROK (in particular, the pleckstrin homology [PH] domain) and in vitro binding assays, we have detected a specific binding interaction between the PH domain of ROK and the cytoplasmic domain of CD44. Scatchard plot analysis indicates that there is a single high\u2010affinity CD44 binding site in the PH domain of ROK with an apparent dissociation constant (Kd) of 1.76 nM, which is comparable to CD44 binding (Kd \u223c1.56 nM) to intact ROK. These findings suggest that the PH domain is the primary ROK binding region for CD44. Furthermore, HA binding to GM7372A cells promotes RhoA\u2010mediated ROK activity, which, in turn, increases phosphorylation of three different inositol 1, 4, 5\u2010trisphosphate receptors (IP<jats:sub>3<\/jats:sub>Rs) [in particular, subtype 1 (IP<jats:sub>3<\/jats:sub>R1), and to a lesser extent subtype 2 (IP<jats:sub>3<\/jats:sub>R2) and subtype 3 (IP<jats:sub>3<\/jats:sub>R3)] all known as IP<jats:sub>3<\/jats:sub>\u2010gated Ca<jats:sup>2+<\/jats:sup> channels. The phosphorylated IP<jats:sub>3<\/jats:sub>R1 (but not IP<jats:sub>3<\/jats:sub>R2 or IP<jats:sub>3<\/jats:sub>R3) is enhanced in its binding to IP<jats:sub>3<\/jats:sub> which subsequently stimulates IP<jats:sub>3<\/jats:sub>\u2010mediated Ca<jats:sup>2+<\/jats:sup> flux. Transfection of the endothelial cells with ROK's PH cDNA significantly reduces ROK association with CD44v10, and effectively inhibits ROK\u2010mediated phosphorylation of IP<jats:sub>3<\/jats:sub>Rs and IP<jats:sub>3<\/jats:sub>R\u2010mediated Ca<jats:sup>2+<\/jats:sup> flux in vitro. The PH domain of ROK also functions as a dominant\u2010negative mutant in vivo to block HA\u2010dependent, CD44v10\u2010specific intracellular Ca<jats:sup>2+<\/jats:sup> mobilization and endothelial cell migration. Taken together, we believe that CD44v10 interaction with ROK plays a pivotal role in IP<jats:sub>3<\/jats:sub>R\u2010mediated Ca<jats:sup>2+<\/jats:sup> signaling during HA\u2010mediated endothelial cell migration. Cell Motil. Cytoskeleton 53:293\u2013316, 2002. \u00a9 2002 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/cm.10078","type":"journal-article","created":{"date-parts":[[2002,10,14]],"date-time":"2002-10-14T16:41:24Z","timestamp":1034613684000},"page":"293-316","source":"Crossref","is-referenced-by-count":66,"title":["CD44v10 interaction with Rho\u2010kinase (ROK) activates inositol 1,4,5\u2010triphosphate (IP<sub>3<\/sub>) receptor\u2010mediated Ca<sup>2+<\/sup> signaling during hyaluronan (HA)\u2010induced endothelial cell migration"],"prefix":"10.1002","volume":"53","author":[{"given":"Patrick A.","family":"Singleton","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lilly 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