PARD6A is a regulator of epithelial cell polarity and tight-junction assembly
TGFBRI is localized to tight junctions where PARD6A is also found. TGFBR1 binds to PARD6A and localizes to tight junctions irrespective of TGF-beta stimulation.
The N-terminus of PARD6A, containing a PB1 domain necessary for binding to TGFBR1
TGFB stimulation induces redistribution of TGFBRII into tight junctions.
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.
In compartment: Nucleus
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