Haemopoietic growth factor regulation of protein kinases and genes associated with cell proliferation.
Haemopoietic growth factors stimulate a number of common biochemical and molecular events despite the high specificity of individual ligand-receptor interactions. Analysis of three distinct colony-stimulating factors (CSFs), interleukin 3 (IL-3), granulocyte-CSF and granulocyte macrophage-CSF, and the lymphocytotropic growth factor IL-2 revealed remarkably similar distal subcellular biochemical signals, although the mode of initial membrane signal transduction may differ significantly. Both early progenitor cell growth factors, such as IL-3, and late-acting factors, such as CSF-1, stimulate tyrosine and serine/threonine substrate phosphorylations. One substrate (p68) is phosphorylated in response to many CSFs and to IL-2, suggesting that it plays a highly conserved role in the signal transduction processes of many different receptor(s). The proliferative CSFs and IL-2 also stimulate the expression of many of the same genes, including protooncogenes, the ornithine decarboxylase gene, and members of the phylogenetically ancient family of stress response genes. Thus although initial membrane events may differ among the proliferative stimulants, the biochemical and molecular convergence of signalling pathways on highly conserved cellular substrates and on the programme of gene expression is seen.
Farrar
W L
WL
Laboratory of Molecular Immunoregulation, National Cancer Institute, Frederick, Maryland.
Ferris
D K
DK
Linnekin
D
D
D002460:Cell Line; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects* / Q000502:physiology; D006133:Growth Substances / Q000502:physiology*; D006410:Hematopoiesis / Q000187:drug effects*; D016298:Hematopoietic Cell Growth Factors; D006801:Humans; D007951:Leukemia, Myeloid / Q000473:pathology; D009955:Ornithine Decarboxylase / Q000235:genetics; D011494:Protein Kinases / Q000378:metabolism* / Q000502:physiology; D011519:Proto-Oncogenes / Q000235:genetics
D006133:Growth Substances; D016298:Hematopoietic Cell Growth Factors; D011494:Protein Kinases; D009955:Ornithine Decarboxylase