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- W2022098276 abstract "Abstract Transforming growth factor‐β (TGFβ) is a key regulator of cell proliferation, death, migration, and differentiation. To explore mechanisms of TGFβ action, we performed systemic analysis of functional dependencies between 153 proteins which changed their expression and synthesis upon treatment of human breast epithelial cells with TGFβ1. We found that TGFβ1 initiated signaling via a scale‐free network of proteins which affect primary cellular metabolism, stress response, signal transduction, transport, transcription, cytoskeleton, and cell death. Multiple inputs into each functional domain were observed, emphasizing robustness of TGFβ1 signaling. Network analysis demonstrated importance of a Plag1/CNK1/RASSF1A/Src‐dependent prozone effect, as a systemic feature which is crucial for TGFβ1‐dependent activation of Erk1/2 and regulation of cell proliferation. We showed that the balance between Plag1, CNK1, RASSF1A and Src defined whether TGFβ1 will stimulate, inhibit or will have no effect on a long‐term activation of Erk1/2 and subsequent TGFβ1 inhibitory or stimulatory effect on cell proliferation. This is the first demonstration of importance of systemic features for incorporation of Erk1/2 activation into TGFβ1 signaling." @default.
- W2022098276 created "2016-06-24" @default.
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- W2022098276 date "2008-10-28" @default.
- W2022098276 modified "2023-09-30" @default.
- W2022098276 title "Systemic analysis of TGFβ proteomics revealed involvement of Plag1/CNK1/RASSF1A/Src network in TGFβ1-dependent activation of Erk1/2 and cell proliferation" @default.
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- W2022098276 doi "https://doi.org/10.1002/pmic.200700960" @default.
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