Journal article

Publication year: 2015

Pages: 3962-3973

Journal: Molecular and Cellular Biology

Volume number: 35

Issue number: 23

ISSN: 0270-7306

eISSN: 1098-5549

Open access status: Green

DOI Link: https://doi.org/10.1128/MCB.00813-15

Publisher: Taylor and Francis Group

Abstract: 
The c-Jun amino-terminal kinase (JNK) plays a role in inflammation, proliferation, apoptosis, and cell adhesion and cell migration by phosphorylating paxillin and beta-catenin. JNK phosphorylation downstream of AMP-activated protein kinase (AMPK) activation is required for high CO2 (hypercapnia)-induced Na,K-ATPase endocytosis in alveolar epithelial cells. Here, we provide evidence that during hypercapnia, JNK promotes the phosphorylation of LMO7b, a scaffolding protein, in vitro and in intact cells. LMO7b phosphorylation was blocked by exposing the cells to the JNK inhibitor SP600125 and by infecting cells with dominant-negative JNK or AMPK adenovirus. The knockdown of the endogenous LMO7b or overexpression of mutated LMO7b with alanine substitutions of five potential JNK phosphorylation sites (LMO7b-5SA) or only Ser-1295 rescued both LMO7b phosphorylation and the hypercapnia-induced Na,K-ATPase endocytosis. Moreover, high CO2 promoted the colocalization and interaction of LMO7b and the Na,K-ATPase alpha(1) subunit at the plasma membrane, which were prevented by SP600125 or by transfecting cells with LMO7b-5SA. Collectively, our data suggest that hypercapnia leads to JNK-induced LMO7b phosphorylation at Ser-1295, which facilitates the interaction of LMO7b with Na,K-ATPase at the plasma membrane promoting the endocytosis of Na,K-ATPase in alveolar epithelial cells.

Harvard Citation style: Dada, L., Bittar, H., Welch, L., Vagin, O., Deiss-Yehiely, N., Kelly, A., et al. (2015) High CO₂ Leads to Na,K-ATPase Endocytosis via c-Jun Amino-Terminal Kinase-Induced LMO7b Phosphorylation, Molecular and Cellular Biology, 35(23), pp. 3962-3973. https://doi.org/10.1128/MCB.00813-15

APA Citation style: Dada, L., Bittar, H., Welch, L., Vagin, O., Deiss-Yehiely, N., Kelly, A., Baker, M., Capri, J., Cohn, W., Whitelegge, J., Vadasz, I., Gruenbaum, Y., & Sznajder, J. (2015). High CO₂ Leads to Na,K-ATPase Endocytosis via c-Jun Amino-Terminal Kinase-Induced LMO7b Phosphorylation. Molecular and Cellular Biology. 35(23), 3962-3973. https://doi.org/10.1128/MCB.00813-15