IL-2 and EGF receptors stimulate the hematopoietic cell cycle via different signaling pathways: demonstration of a novel role for c-myc.
Stimulation via cytokine receptors such as IL-2 and IL-3 receptors, but not by the EGF receptor (EGFR), induces cells of the BAF-B03 hematopoietic cell line to transit the cell cycle. We demonstrate that the IL-2 receptor beta chain (IL-2R beta) is linked to at least two intracellular signaling pathways. One pathway may involve a protein tyrosine kinase of the src family, which leads to the induction of the c-jun and c-fos genes, among others. A second pathway, involving an as yet unknown mechanism, leads to c-myc gene induction. Stimulation of the EGFR, expressed following transfection of an appropriate recombinant construct, can activate the former, but not the latter, pathway in this cell line and cause the cells to enter S phase but not progress further. This deficiency can be rescued by ectopic expression of the c-myc gene, indicating a novel role for this proto-oncogene in the S to G2/M transition of the cell cycle.
Shibuya
H
H
Institute for Molecular and Cellular Biology, Osaka University, Japan.
Yoneyama
M
M
Ninomiya-Tsuji
J
J
Matsumoto
K
K
Taniguchi
T
T
D000818:Animals; D016203:CDC2 Protein Kinase / Q000096:biosynthesis; D002453:Cell Cycle / Q000235:genetics; D002460:Cell Line; D016213:Cyclins / Q000096:biosynthesis; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D016259:Genes, myc / Q000502:physiology*; D007376:Interleukin-2 / Q000494:pharmacology*; D051379:Mice; D015398:Signal Transduction; D015533:Transcriptional Activation
D016213:Cyclins; D007376:Interleukin-2; D004815:Epidermal Growth Factor; D016203:CDC2 Protein Kinase