Membrane protein polarity defects in Autosomal Dominant (AD) PKD include the mis-polarization of normally basolateral membrane proteins to apical, lumenal membranes, such as epidermal growth factor (EGFR/ErbB) receptors and Na(+)K(+)-ATPase-α1 subunit; mis-polarization of normally apical membrane proteins to basolateral membranes, including the Na(+)K(+)2Cl(-) (NKCC1) symporter; and the failure to traffic and insert proteins into membranes resulting in their intracellular accumulation, such as E-cadherin and the β1 subunit of Na(+)K(+)-ATPase.
Enhancing EGFR/PKC signaling may reverse the MMP-9 unfavorable dimerization patterns and thereby promote uteroplacental and vascular remodeling in preeclampsia.
The altered regulation of ERBBs and their effectors in PKD is influenced by enhanced activity of SRC kinase, which is promoted by the loss of cytoplasmic Ca<sup>2+</sup> and an increase in cAMP-dependent PKA kinase activity that stimulates CFTR, driving the secretory phenotype of ADPKD.