Abstract
Transforming growth factors-beta (TGF-βs) play pivotal roles in the regulation of cell growth and differentiation, although little is known regarding the regulation of cytoplasmic components by TGF-βs. Src tyrosine kinase is required for signal transduction of various cytokine receptors, including epidermal growth factor (EGF), platelet-derived growth factor (PDGF), and G-protein coupled receptors. Moreover, Src tyrosine kinase is important in signal cross-talk between these receptors. To determine whether Src kinase is also involved in TGF-β signaling, we examined the effects of TGF-β1 on Src in the rat fibroblast cell line 3Y1 and in v-Src-transformed 3Y1 (SR-3Y1). TGF-β1 inhibited mitogen-activated protein kinase activity and inhibited growth in SR-3Y1 cells, while it did not affect the growth of 3Y1 cells. TGF-β1 significantly decreased v-Src kinase activity and protein abundance in SR-3Y1 cells, mainly by accelerating the degradation of v-Src. In contrast, in 3Y1 cells, TGF-β1 did not affect c-Src abundance or kinase activity. However, upon activation of c-Src in 3Y1 cells by PDGF, TGF-β1 decreased Src abundance. Additionally, in 3Y1 cells transfected with an activated c-Src mutant which lacks the SH3 domain, its level was decreased by TGF-β1 treatment. These findings suggest that TGF-β1 specifically induces degradation of activated Src kinase. This may be a novel mechanism for cross-talk between growth factors and TGF-β.
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Fukuda, K., Kawata, S., Tamura, S. et al. Transforming growth factor-β1-induced degradation of activated Src tyrosine kinase in rat fibroblasts. Oncogene 16, 3349–3356 (1998). https://doi.org/10.1038/sj.onc.1201896
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DOI: https://doi.org/10.1038/sj.onc.1201896
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