Mechanism of differential inhibition of factor-dependent cell proliferation by transforming growth factor-beta 1: selective uncoupling of FMS from MYC.
Transforming growth factor-beta 1 ( TGF-beta 1) selectively modulates hematopoietic cell proliferation. The proliferation of FDC- P1 clone MAC-11, a factor-dependent murine myeloid progenitor cell line, was inhibited differentially by TGF-beta 1: strongly in macrophage colony-stimulating factor ( M-CSF), mildly in interleukin-3, and not at all in granulocyte-macrophage-CSF ( GM-CSF). Flow cytometry and Western blots showed an unexpected increase in expression of FMS, the receptor for M-CSF, in response to TGF-beta 1. Metabolic labeling with 35S-methionine showed that synthesis of FMS protein accelerated in response to TGF-beta 1, whereas its degradation was unaffected. Northern analyses showed a rapid increase in c-fms RNA after the addition of TGF-beta 1. TGF-beta 1 did not affect kinase activity, cellular phosphotyrosine response, or internalization of FMS. However, TGF-beta 1 inhibited the induction by M-CSF of c-myc RNA analyzed on Northern blots and protein detected by radioimmuno-precipitation. TGF-beta 1 did not affect induction of c-myc expression by GM-CSF or induction of c-fos or c-jun by M-CSF. Therefore, FMS and the GM-CSF receptor induce c-myc via signal transduction pathways that differ in that only the former is inhibited by TGF-beta 1. This inhibition may account for the selective growth regulation by TGF-beta 1.[1]References
- Mechanism of differential inhibition of factor-dependent cell proliferation by transforming growth factor-beta 1: selective uncoupling of FMS from MYC. Chen, A.R., Rohrschneider, L.R. Blood (1993) [Pubmed]
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