TY - JOUR
T1 - High CO2 leads to Na, K-ATPase endocytosis via c-Jun amino-terminal kinase-induced LMO7b phosphorylation
AU - Dada, Laura A.
AU - Trejo Bittar, Humberto E.
AU - Welch, Lynn C.
AU - Vagin, Olga
AU - Deiss-Yehiely, Nimrod
AU - Kelly, Aileen M.
AU - Baker, Mairead R.
AU - Capri, Joseph
AU - Cohn, Whitaker
AU - Whitelegge, Julian P.
AU - Vadász, István
AU - Gruenbaum, Yosef
AU - Sznajder, Jacob I.
N1 - Publisher Copyright:
© 2015, American Society for Microbiology.
PY - 2015
Y1 - 2015
N2 - The c-Jun amino-terminal kinase (JNK) plays a role in inflammation, proliferation, apoptosis, and cell adhesion and cell migration by phosphorylating paxillin and ß-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 α1 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.
AB - The c-Jun amino-terminal kinase (JNK) plays a role in inflammation, proliferation, apoptosis, and cell adhesion and cell migration by phosphorylating paxillin and ß-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 α1 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.
UR - http://www.scopus.com/inward/record.url?scp=84946200964&partnerID=8YFLogxK
U2 - 10.1128/MCB.00813-15
DO - 10.1128/MCB.00813-15
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C2 - 26370512
AN - SCOPUS:84946200964
SN - 0270-7306
VL - 35
SP - 3962
EP - 3973
JO - Molecular and Cellular Biology
JF - Molecular and Cellular Biology
IS - 23
ER -