Death and Baxes: mechanisms of lymphotrophic cytokines.
In this review, we briefly cover the critical requirements for interleukin-7 (IL-7) in thymocyte development and peripheral T-cell homeostasis. Part of the IL-7 effect is antiapoptotic or 'trophic' and we have studied the intracellular pathways involved in lymphocyte survival and death regulated by this cytokine. We review the evidence for a role of the JAK signal transducers and activators of transcription protein (STAT) pathway and phosphoinositide 3-kinase (PI3K)-AKT pathways in survival. The death pathway following IL-7 withdrawal is discussed in terms of the balance of BCL-2 vs. BAX and other death proteins and the role of metabolic disturbances involving glucose metabolism and intracellular pH. The IL-7 survival and death pathways in lymphocytes may be representative of many trophic factors in different cell types; yet we conclude that much of the mechanism remains to be discovered.
Khaled
Annette R
AR
BioMolecular Science Center, Department of Molecular Biology and Microbiology, University of Central Florida, Orlando, FL, USA.
Durum
Scott K
SK
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D006801:Humans; D007377:Interleukin-3 / Q000276:immunology; D015851:Interleukin-7 / Q000276:immunology*; D011518:Proto-Oncogene Proteins / Q000276:immunology*; D019253:Proto-Oncogene Proteins c-bcl-2; D020395:Receptors, Interleukin-7 / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000502:physiology*; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D007377:Interleukin-3; D015851:Interleukin-7; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D020395:Receptors, Interleukin-7; D051028:bcl-2-Associated X Protein