The conserved function of the replication components extends to the clamp loader and processivity clamp as well other functions of the replisome.

The roles of RFC and PCNA are analogous to the E. coli γ clamp loader and β2 processivity unit

TLS Online TPP Program

#Id: 9361

#Unit 4. Cell Communication and Cell Signaling

R-Smads comprising: 

An N-terminal MH1 domain

A central proline-rich linker 

A C-terminal MH2 domain

TLS Online TPP Program

#Id: 9362

#Unit 4. Cell Communication and Cell Signaling

MH1 domain contains:

DNA binding segment Nuclear-localization signal

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#Id: 9363

#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

TLS Online TPP Program

#Id: 9364

#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

TLS Online TPP Program

#Id: 9365

#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

TLS Online TPP Program

#Id: 9366

#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