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Approximately 61,000 statements.
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Akt/PKB is a member of the AGC kinase family, which also includes S6K, RSK, SGK, and PKC (Peterson and Schreiber, 1999; Woodgett, 2005). Most members of this family, including Akt, are phosphorylated at two key residues located at the catalytic site (activation loop or Tloop) and the C-terminal hydrophobic motif (HM) site. Phosphorylation of the HM site promotes docking of the PIF pocket of PDK1 to the HM site and concomitantly leads to the phosphorylation of the T-loop site upon growth factor stimulation and PI3K activation (Biondi, 2004). PDK1 phosphorylates Akt/PKB at Thr308 of its T loop, which is essential for Akt catalytic activity (Alessi et al., 1997; Stephens et al., 1998). As with many members of the AGC kinase family, HM phosphorylation of Akt at Ser473 and T-loop Thr308 phosphorylation has been proposed to be interdependent on each other (Scheid et al., 2002; Toker and Newton, 2000), although there is some opposing evidence (Alessi et al., 1996; Collins et al., 2003; Woodgett, 2005). For example, cells expressing a PDK1 mutant with a defective PIF pocket can still phosphorylate Akt (Biondi et al., 2001; Collins et al., 2003). Moreover, the HM of Akt also displays lower affinity for the PIF pocket of PDK1 in comparison to other PDK1 targets (Frodin et al., 2002). Nevertheless, since dually phosphorylated Akt has higher in vitro kinase activity (Alessi et al., 1996; Scheid et al., 2002), it is presumed that most Akt functions are mediated by the dually phosphorylated Akt.
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2014-07-03T14:33:03.240+02:00
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