SNARE complex is disassembled by ATP-dependent reaction mediated by cytosolic proteins, NSF & α-SNAP

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#Unit 4. Cell Communication and Cell Signaling

Inside the nucleus, R smad-co smad complex binds to nuclear transcription factor TFE3 to activate transcription of PAI-1 & other ECM proteins such as fibronectin & collagens

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#Unit 4. Cell Communication and Cell Signaling

Within the nucleus, R-Smads are modified by:

Phosphorylation of linker domains

Acetylation of MH1 domains

Dephosphorylation of the C-terminal serines by nuclear

phosphatases

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#Unit 4. Cell Communication and Cell Signaling

BMP proteins, activate a different set of receptors that are similar to the TGF-β RI and RII proteins but phosphorylate other R-Smads, Smad1, Smad5, & Smad8

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#Unit 4. Cell Communication and Cell Signaling

Smad4 was originally called DPC (deleted in pancreatic cancer)

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#Unit 4. Cell Communication and Cell Signaling

Negative regulators of TGF-β signaling are induced by TGF-β signaling (Example of Negative feedback): 

Ski 

SnoN 

I-Smads (Smad7)

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#Unit 4. Cell Communication and Cell Signaling

SnoN and Ski trigger abnormal cell proliferation by blocking the Smad-complex.