Molecular events associated with the action of haemopoietic growth factors.
Haemopoietic growth factors stimulate a number of consensus biochemical and molecular events regardless of the specificity detailed by unique ligand and receptor structures. Analysis of three distinct colony stimulating factors, CSFs (IL-3, G-CSF, GM-CSF) and the lymphocytotropic growth factor IL-2 reveal remarkable similar distal subcellular biochemical signals although 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 by many CSF stimulants, including IL-2, suggesting a highly conserved role in many unique receptor(s) signal transduction processes. The proliferative CSFs and IL-2 also stimulate the expression of many of the same genes including proto-oncogenes, ornithine decarboxylase and members of the ancient family of stress response genes. Although initial membrane events may differ among the respective proliferative stimulants, biochemical and molecular convergence on highly conserved cellular substrates and the programme of gene expression is seen.
Farrar
W L
WL
Laboratory of Molecular Immunoregulation, National Cancer Institute, Frederick, MD 21701-1013.
Evans
S W
SW
Harel-Bellan
A
A
Ferris
D K
DK
D000818:Animals; D002460:Cell Line; D003115:Colony-Stimulating Factors / Q000494:pharmacology; D015180:Electrophoresis, Gel, Two-Dimensional; D005786:Gene Expression Regulation; D006131:Growth Inhibitors / Q000494:pharmacology; D006133:Growth Substances / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology; D051379:Mice; D010766:Phosphorylation; D011506:Proteins / Q000378:metabolism; D015398:Signal Transduction
D003115:Colony-Stimulating Factors; D006131:Growth Inhibitors; D006133:Growth Substances; D007376:Interleukin-2; D011506:Proteins