Role of activin A in negative regulation of normal and tumor B lymphocytes.
Activin A, a member of the transforming growth factor beta superfamily, has a wide spread expression pattern and pleiotropic functions. In this overview we summarize data that points to a role of activin A in negative regulation of B lineage lymphocytes. Experiments performed by us and by other groups revealed the capacity of activin A to cause apoptotic death of tumor myeloma cells, through mechanisms of cell cycle inhibition and antagonism with the survival signal of interleukin-6. In vitro studies on B lymphocyte generation from bone marrow stem cells and use of human nasal polyps as a model of inflamed tissue further demonstrate an inhibitory role of activin A in B cell spread and accumulation. These data are analyzed with respect to our model of tissue organization that we term the "restrictin model of cell growth regulation." This model assumes a morphogen-like role of activin A in the hematopoietic system. Thus, the relative concentration of biologically functional activin A, in different parts of the tissue, may determine the local B cell content and functional state of these cells within a specific microenvironment.
Zipori
D
D
Department of Molecular Cell Biology, the Weizmann Institute of Science, Rehovot, Israel. dov.zipori@weizmann.ac.il
Barda-Saad
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M
D028341:Activins; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001402:B-Lymphocytes / Q000166:cytology* / Q000187:drug effects; D001854:Bone Marrow Cells / Q000166:cytology; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects; D038681:Follistatin; D006023:Glycoproteins / Q000096:biosynthesis; D006131:Growth Inhibitors; D006410:Hematopoiesis / Q000187:drug effects / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects; D006801:Humans; D007265:Inhibins / Q000096:biosynthesis / Q000494:pharmacology / Q000502:physiology*; D036341:Intercellular Signaling Peptides and Proteins; D015850:Interleukin-6 / Q000502:physiology; D004915:Leukemia, Erythroblastic, Acute / Q000473:pathology; D008954:Models, Biological; D009101:Multiple Myeloma / Q000473:pathology; D009298:Nasal Polyps / Q000276:immunology / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000166:cytology* / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D017154:Stromal Cells / Q000378:metabolism*
D038681:Follistatin; D006023:Glycoproteins; D006131:Growth Inhibitors; D036341:Intercellular Signaling Peptides and Proteins; D015850:Interleukin-6; C069698:restrictin-P; D028341:Activins; D007265:Inhibins