tailieunhanh - Báo cáo khoa học: Death-associated protein kinase (DAPK) and signal transduction: additional roles beyond cell death

Death-associated protein kinase (DAPK) is a stress-regulated protein kinase that mediates a range of processes, including signal-induced cell death and autophagy. Although the kinase domain of DAPK has a range of substrates that mediate its signalling, the additional protein interaction domains of DAPK are relatively ill defined. | MINIREVIEW Death-associated protein kinase DAPK and signal transduction additional roles beyond cell death Yao Lin Ted R. Hupp and Craig Stevens CRUK p53 SignalTransduction Laboratories Institute of Genetics and Molecular Medicine University of Edinburgh UK Keywords autophagy DAPK growth factor immune response interactome kinase mTOR peptide Correspondence C. Stevens CRUK p53 SignalTransduction Laboratories Institute of Genetics and Molecular Medicine University of Edinburgh Edinburgh EH4 2XR UK E-mail Received 11 March 2009 revised 12 August 2009 accepted 8 September 2009 doi Death-associated protein kinase DAPK is a stress-regulated protein kinase that mediates a range of processes including signal-induced cell death and autophagy. Although the kinase domain of DAPK has a range of substrates that mediate its signalling the additional protein interaction domains of DAPK are relatively ill defined. This review will summarize our current knowledge of the DAPK interactome the use of peptide aptamers to define novel protein-protein interaction motifs and how these new protein-protein interactions give insight into DAPK functions in diverse cellular processes including growth factor signalling the regulation of autophagy and its emerging role in the regulation of immune responses. Introduction Death-associated protein kinase-1 DAPK-1 is the prototypic member of a family of death-related kinases that includes DAPK-1-related protein 1 also named DAPK-2 Zipper interacting kinase ZIPK also named DAPK-3 DAP kinase related apoptosis inducing protein kinase 1 DRAK1 and DRAK2 1 . These kinases share a high degree of homology in their catalytic domains. However the extracatalytic domains and biological function of these five proteins differ markedly 1 . DAPK a calcium calmodulin CaM -regulated Ser Thr protein kinase was originally identified as a factor that regulates apoptosis in response to the death-inducing cytokine .