Though the caveolin-1 association with PDK1 contributes to PDK1 function via the mediation of its subcellular localization, it remains to be seen whether the differences in PDK1 subcellular localization are due to the differences in cell lines or to differences in the function of PDK1. Because PDK1 also contains a PH domain in its C-terminus which binds to the inositol ring of PIP2 and 3, PDK1 appears to be localized predominantly in the ‘harpagoside.html’>19210-12-9 membrane, depending on the activity of PI3K activity  and . However, contractively, other data reported that the PDK1 activity was stimulated in a PI3K-independent manner upon treatment with growth factors and chemokines . In addition, the subcellular localization of PDK1 was also unaffected by treatment with growth factors and chemokines. According to their results, stimulation with IGF-1 caused no further activation or plasma membrane localization of PDK1, and PDK1 was thought to be constitutively active . Further, our confocal data demonstrated that PDK1 cav, containing the intact PH domain, is predominantly localized proximally to the nuclear membrane, rather than the plasma membrane (Fig. 2F). Thus, though it remains unclear as to the mechanism by which the PH domain of PDK1 contributes to the mediation of its kinase activity and plasma membrane localization, the interaction between PDK1 and caveolin-1 may also contribute to the localization of PDK1 to the plasma membrane (Figs. 2E and F). It has been reported that the overexpression, and/or constitutive activation of PDK1, results in oncogenic transformation, culminating in the progression to invasive and metastatic phenotypes . In addition, it has been documented that PDK1 ‘http://en.wikipedia.org/wiki/Expression’>expression and activity are up-regulated in several types of cancers ,  and . However, it remains to be determined whether or not dysfunctions with regard to the interactions occurring between PDK1 and caveolin-1 are related to these diseases.