Adeno-associated vectors (AAV) Adeno-associated viruses (AAVs) are a group of small, single-stranded DNA viruses. The insert size for AAV is 4.5 kb, with the advantage of long-term gene expression as they integrate into chromosomal DNA.

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#Unit 4. Cell Communication and Cell Signaling

MH1 domain contains:

DNA binding segment Nuclear-localization signal

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#Unit 4. Cell Communication and Cell Signaling

Phosphorylation of two serines in Ser-X-Ser motif at the extreme C-terminus of the MH2 domain by the activated RI separates the two domains, exposing the NLS for binding to importins

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#Unit 4. Cell Communication and Cell Signaling

Simultaneously, two serines in each Smad2/3 phosphorylated by RI receptor kinase bind to phosphoserine-binding sites in the MH2 domains of a Smad4

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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