chapter  3
Signaling Pathways in Mammalian Autophagy
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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.