Homeostatic control of lymphocyte survival: potential origins and implications.
Lymphocytes depend on extracellular ligands to maintain their viability. Structurally diverse lymphocyte receptors transmit survival signals through separate signal transduction cascades, which all share the ability to sustain viability by maintaining the sequestration of apoptogenic factors within mitochondria. Receptors can induce cellular survival either by promoting the expression and/or function of anti-apoptotic Bcl-2 family proteins or by activating the phosphatidylinositol-3 kinase Akt pathway. Either of these events represses the function of the pro-apoptotic proteins Bax and Bak, which are required for mitochondrial release of cytochrome c. As we discuss here, the apparently redundant functions of Bax and Bak may have evolved to prevent lymphocyte mitochondria from adapting to loss of receptor mediated signal transduction and thus keep lymphocytes from accumulating in a cell-autonomous manner.
Plas
David R
DR
Abramson Family Cancer Research Institute and Department of Cancer Biology, University of Pennsylvania, Philadelphia, PA 19104, USA.
Rathmell
Jeffrey C
JC
Thompson
Craig B
CB
D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002470:Cell Survival; D016207:Cytokines / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D008214:Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D018448:Models, Immunological; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2; D011946:Receptors, Antigen / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism; D015398:Signal Transduction; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein
C494772:BAK1 protein, human; C494826:BAX protein, human; D015815:Cell Adhesion Molecules; D016207:Cytokines; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011946:Receptors, Antigen; D011971:Receptors, Immunologic; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; D005947:Glucose