Abstract
14-3-3 proteins exert an extraordinarily widespread influence on cellular processes in all eukaryotes. They operate by binding to specific phosphorylated sites on diverse target proteins, thereby forcing conformational changes or influencing interactions between their targets and other molecules. In these ways, 14-3-3s ‘finish the job’ when phosphorylation alone lacks the power to drive changes in the activities of intracellular proteins. By interacting dynamically with phosphorylated proteins, 14-3-3s often trigger events that promote cell survival – in situations from preventing metabolic imbalances caused by sudden darkness in leaves to mammalian cell-survival responses to growth factors. Recent work linking specific 14-3-3 isoforms to genetic disorders and cancers, and the cellular effects of 14-3-3 agonists and antagonists, indicate that the cellular complement of 14-3-3 proteins may integrate the specificity and strength of signalling through to different cellular responses.
- 14-3-3 protein
- cancer
- cell signalling
- neurodegenerative disorder
- plant
- protein kinase B (PKB)
Abbreviations: AANAT, arylalkamine/serotonin N-acetyltransferase; BAD, Bcl-2/Bcl-XL-antagonist, causing cell death; BSE, bovine spongiform encephalopathy; Cdc, cell-division cycle; CDK, cyclin-dependent kinase; chk, checkpoint kinase; CJD, Creutzfeldt–Jakob disease; COPI, coatamer I; CSF, cerebrospinal fluid; ER, endoplasmic reticulum; ERK, extracellular-signal-regulated kinase; FKHR, Forkhead in rhabdomyosarcoma; FOXO, Forkhead box, class O; HCV, hepatitis C virus; IRS-1, insulin receptor substrate-1; LR, axis, left–right axis; MAPK, mitogen-activated protein kinase; MDS, Miller–Dieker syndrome; NLS, nuclear localization signal; NR, nitrate reductase; PDE3B, phosphodiesterase 3B; PI3K, phosphoinositide 3-kinase; PKA, protein kinase A; PKB, protein kinase B; PKC, protein kinase C; SCA, spinocerebellar ataxia; SH2, Src homology 2; SnRK, SNF1-related kinase; TSE, transmissible spongiform encephalopathy; WPK4, wheat protein kinase 4
- The Biochemical Society, London