There is general agreement that amino acids, in contrast to insulin, are not able to stimulate protein kinase В phosphorylation and activity/ 3,54 Controversy, however, exists as to whether or not amino acids can stimulate Ptdlns 3-kinase activity, because direct attempts to show this failed55'57 or the observed stimulation was transient.58 ,59 By contrast, amino acid-dependent, mTOR-mediated protein phosphorylation was sensitive to Ptdlns 3-kinase inhibitors, as first shown by Blommaart et al60 and later confirmed by others (for review see refs. 53, 54). Al though it has been argued in the literature that Ptdlns 3-kinase inhibitors are not specific and may also inhibit mTOR directly, this was considered unlikely.54 Rather, it may be that mTOR-mediated signaling and Ptdlns 3-kinase-mediated signaling (perhaps via PDK1) are on parallel pathways and that both pathways are required to phosphorylate downstream tar gets, such as p70S6 kinase, at different positions before full activation is obtained.61'63 Because
16. Kihara A, Kabeya Y, Ohsumi Y et al. Beclin-phosphatidylinositol 3-kinase complex functions at the trans-Golgi network. EMBO Rep 2001; 2:330-335.