NEDD4L, Phosphorylated (Ser342) (Neural precursor cell expressed, developmentally down-regulated 4-like, E3 ubiquitin-protein ligase NEDD4-like, FLJ33870, hNedd4-2, KIAA0439, NEDD4.2, Nedd4-2, NEDD4-2, NEDL3, RSP5)

NEDD4 (neural precursor expressed, developmentally down-regulated protein 4) was originally identified as a gene that is highly expressed in the early mouse embryonic central nervous system (1). More recently, a family of NEDD4-like proteins has been defined that includes seven members in humans (2). NEDD4 and NEDD4-like (NEDD4L) proteins contain multiple functional domains including a calcium-dependent phospholipid and membrane binding domain (C2 domain), two to four protein binding domains (WW domains), and an E3 ubiquitin-protein ligase domain (HECT domain). NEDD4 and NEDD4L have been shown to downregulate both neuronal voltage-gated Na+ channels (NaVs) and epithelial Na+ channels (ENaCs) in response to increased intracellular Na+ concentrations (3,4). The WW domains of NEDD4 bind to PY motifs (amino acid sequence PPXY) found in multiple NaV and ENaC proteins; ubiquitination of these proteins is mediated by the HECT domain of NEDD4 and results in their internalization and removal from the plasma membrane. Mutation of the PY motifs in ENaC proteins is associated with Liddle's Syndrome, an autosomal-dominant form of hypertension (5). In addition to targeting sodium channels, NEDD4L has also been shown to negatively regulate TGF-b signaling by targeting Smad2 for degradation (6). Mouse and human NEDD4 are rapidly cleaved by caspase proteins during apoptosis, although the significance of this cleavage is not clear (7).\nNEDD4L can be phosphorylated at Ser342 and Ser448 by several AGC kinase family members including SGK1, Akt and PKA (8-11). Phosphorylation at these sites inhibits NEDD4L function as a suppressor of ENaCs and as a regulator of TGF-b signaling through its effects on Smad2/3 binding (8-11).\n\nApplications:\nSuitable for use in Western Blot. Other applications not tested.\n\nRecommended Dilution:\nWestern Blot: 1:1000\nOptimal dilutions to be determined by the researcher.\n\nStorage and Stability:\nMay be stored at 4 degrees C for short-term only. For long-term storage and to avoid repeated freezing and thawing, aliquot and store at -20 degrees C. Aliquots are stable for at least 12 months at -20 degrees C. For maximum recovery of product, centrifuge the original vial after thawing and prior to removing the cap. Further dilutions can be made in assay buffer.

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