Abstract:
:Protein kinase B/Akt plays crucial roles in promoting cell survival and mediating insulin responses. The enzyme is stimulated by phosphorylation at two regulatory sites: Thr 309 of the activation segment and Ser 474 of the hydrophobic motif, a conserved feature of many AGC kinases. Analysis of the crystal structures of the unphosphorylated and Thr 309 phosphorylated states of the PKB kinase domain provides a molecular explanation for regulation by Ser 474 phosphorylation. Activation by Ser 474 phosphorylation occurs via a disorder to order transition of the alphaC helix with concomitant restructuring of the activation segment and reconfiguration of the kinase bilobal structure. These conformational changes are mediated by a phosphorylation-promoted interaction of the hydrophobic motif with a channel on the N-terminal lobe induced by the ordered alphaC helix and are mimicked by peptides corresponding to the hydrophobic motif of PKB and potently by the hydrophobic motif of PRK2.
journal_name
Mol Celljournal_title
Molecular cellauthors
Yang J,Cron P,Thompson V,Good VM,Hess D,Hemmings BA,Barford Ddoi
10.1016/s1097-2765(02)00550-6subject
Has Abstractpub_date
2002-06-01 00:00:00pages
1227-40issue
6eissn
1097-2765issn
1097-4164pii
S1097-2765(02)00550-6journal_volume
9pub_type
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