Protein kinase B/Akt at a glance.

Among the signalling proteins that respond to a large variety of signals, protein kinase B (PKB, also known as Akt) appears to be a central player in regulation of metabolism, cell survival, motility, transcription and cell-cycle progression. Conserved from primitive metazoans to humans, PKB belongs to the AGC subfamily of the protein kinase superfamily, which consists of 518 members in humans (Manning et al., 2002). PKB and v-AKT were first cloned in 1991 by three independent groups (Brazil and Hemmings, 2001), more than a decade after the original identification of transforming murine leukemia virus Akt8 (Staal et al., 1977). The PKB subfamily comprises three mammalian isoforms, PKB , PKB and PKB (Akt1, Akt2 and Akt3, respectively), which are products of distinct genes and share a conserved structure that includes three functional domains: an N-terminal pleckstrin homology (PH) domain, a central kinase domain, and a C-terminal regulatory domain containing the hydrophobic motif (HM) phosphorylation site [FxxF(S/T)Y] (Hanada et al., 2004). This architecture is conserved among species from fly, worm, mouse to man. Both the central kinase domain and the HM are highly conserved among AGC members, such as protein kinase C, ribosomal p90 S6 kinase, serumand glucocorticoid-induced kinase, and p70 S6 kinase, mediators of responses triggered by insulin and/or other growth factors. Interestingly, the PH domain, essential for binding to lipids such as PtdIns(3,4,5)P3, is absent in the S. cerevisiae orthologue (Sch9).