Reaction heterodimer_association e_re343
Occludin*:PARD6A|S345_pho:TGFB1|hm2:TGFBR1|Ser_pho|hm2:TGFBR2|Ser_pho|hm2@Cytoplasm + SMURF1@Cytoplasm → PARD6A|S345_pho:SMURF1@Cytoplasm
No reaction regulators
SMURF1 is an homologous to E6AP C-ter (HECT)-type E3 ubiquitin ligase
SMURF1 performs a crucial role in the regulation of the BMP signalling pathway in both embryonic development and bone remodelling.
PARD6A interacts with TGFB receptors and is phsophorylated by TGFBRIII.
Phosphorylation of Par6 is required for TGFB-dependent EMT in mammary gland epithelial cells
This phosphorylation controls the interaction of PARD6A with the E3 ubiquitin ligase Smurf1.
Smurf1, in turn, targets GTPase RhoA for degradation, thereby leading to a loss of tight junctions.
Signaling molecules act directly on polarity proteins, bypassing transcription factors such as Snail and Zeb1:
TGFBRI binds to the tight junction protein Occludin and locally assembles into a complex containing Par6.
Activated TGFBRII phosphorylates Par6, which binds to Smurf1 and causes RhoA ubiquitylation and the dissolution of junctions.