Serine/threonine protein kinases and apoptosis

Over the past decade, our understanding of apoptosis, or programmed cell de ath, has increased greatly, with the identification of some of the major co mponents of the apoptotic programme and the processes regulating their acti vation. Although apoptosis is an intrinsic process present in all cells, it can be regulated by extrinsic factors, including hormones, growth factors, cell surface receptors, and cellular stress. The actions of both pro- and antiapoptotic factors are of ten affected by modulation of the phosphorylat ion status of key elements of the apoptotic process. This minireview ct wil l focus on the role of protein kinases in apoptosis. Apoptosis is a multist ep process and protein kinases have been implicated both in the upstream in duction phase of apoptosis and in the downstream execution stage, as the di rect targets for caspases. Due to the space constraints of this review it i s not possible to discuss all of the kinases involved in the apoptotic proc ess and we have focused here on the role of the serine/threonine protein ki nases. The kinases of this family that have been suggested to play a role i n apoptosis are the mitogen-activated protein kinase (MAPK) family, specifi cally p42/44 ERK, p38 MAPK and c-Jun N-terminal kinase (JNK), cyclic AMP-de pendent protein kinase (PKA), protein kinase B (PKB), or Akt and protein ki nase C (PKC). me have also considered briefly the potential for the regulat ion of these kinases by tyrosine protein kinases, such as c-abl. (C) 2000 A cademic Press.