The pims and outs of survival signaling: role for the Pim-2 protein kinase in the suppression of apoptosis by cytokines
- Howard Hughes Medical Institute, Center for Advanced Biotechnology and Medicine, Department of Molecular Biology and Biochemistry, Cancer Institute of New Jersey, Rutgers University, Piscataway, New Jersey 08854, USA
This extract was created in the absence of an abstract.
The regulation of cell survival has a well-documented role in the maintenance of homeostasis, the damage response, and is misregulated in various disease states. Cancer, in particular, is one disease in which the failure to maintain an intact apoptotic response is associated with disease progression and treatment failure (Cory and Adams 2002). Apoptosis is regulated, in part, through dependence upon growth factors and cytokines. For example, the survival of lymphoid cells is closely controlled by specific cytokines, which provide an intricate selection process to determine the cells that should be maintained and those that should not. Whereas this cytokine and growth factor addiction can be thought of as an effective means for controlling populations of normal proliferating cells, cells do occasionally escape this dependence, often through specific defects in the capacity to undergo apoptosis, or the upstream signal transduction pathways that regulate apoptosis, and the result can be tumorigenesis. Thus, understanding how the cytokine and growth factor signaling pathways regulate survival is an integral step toward the development of effective cancer treatments.
Growth factors and cytokines signal survival through their cognate receptors, activating signaling pathways often composed of protein kinase cascades, the most notorious of which include the Map kinases, Jak/Stat, PI3 kinase/Akt, and IKK/NFκB. Through the phosphorylation of specific substrates, survival activity can be manifest in a myriad of ways spanning regulation of transcription through direct modification of apoptotic effectors.
There are a large number of growth factors and cytokines, some of which provide survival signals specific to certain cell types, whereas others posses more ubiquitous survival functions. Many share a number of common kinase signaling pathways, and it is merely the mechanism of pathway activation that determines specificity of the survival signal. There is also cross-talk, overlap, and redundancy to many survival signaling pathways that impose layers of …
