60kDa lysophospholipase, a new Sgk1 molecular partner involved in the regulation of ENaC.
The serum- and glucocorticoid-regulated kinase (Sgk1) is essential for hormonal regulation of ENaC-mediated sodium transport and is involved in the transduction of growth-factor-dependent cell survival and proliferation. The identification of molecular partners for Sgk1 is crucial for the understanding of its mechanisms of action. We performed a yeast two-hybrid screening based on a human kidney cDNA library to identify molecular partners of Sgk1. As a result the screening revealed a specific interaction between Sgk1 and a 60 kDa Lysophospholipase (LysoLP). LysoLP is a poorly characterized enzyme that, based on sequence analysis, might possess lysophospholipase and asparaginase activities. We demonstrate that LysoLP has indeed a lysophospholipase activity and affects metabolic functions related to cell proliferation and regulation of membrane channels. Moreover we demonstrate in the Xenopus oocyte expression system that LysoLP downregulates basal and Sgk1-dependent ENaC activity. In conclusion LysoLP may represent a new player in the regulation of ENaC and Sgk1-dependent signaling.
Dipartimento di Medicina Sperimentale e Clinica G. Salvatore, Università Magna Graecia, Catanzaro, Italy.
Miranda
M
Menniti
Rodolfo
R
Iuliano
Michael
M
Föller
Mentor
M
Sopjani
Ioana
I
Alesutan
Stefania
S
Mariggiò
Charity
C
Nofziger
Angela M
AM
Perri
Rosario
R
Amato
Bonnie
B
Blazer-Yost
Daniela
D
Corda
Florian
F
Lang
Nicola
N
Perrotti
D000818:Animals; D002460:Cell Line; D015536:Down-Regulation; D053503:Epithelial Sodium Channels / Q000378:metabolism*; D015723:Gene Library; D006801:Humans; D017874:Immediate-Early Proteins / Q000378:metabolism*; D008245:Lysophospholipase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009865:Oocytes / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D015398:Signal Transduction; D020798:Two-Hybrid System Techniques; D014981:Xenopus / Q000254:growth & development; D000099184:Serum-Glucocorticoid Regulated Kinases
D053503:Epithelial Sodium Channels; D017874:Immediate-Early Proteins; D008245:Lysophospholipase; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D017346:Protein Serine-Threonine Kinases; D000099184:Serum-Glucocorticoid Regulated Kinases