Curated Information
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Home > Curated Information Page > PubMed Id: 25480791
Chen T, et al. (2015) Cyclic GMP kinase II (cGKII) inhibits NHE3 by altering its trafficking and phosphorylating NHE3 at three required sites: identification of a multifunctional phosphorylation site. J Biol Chem 290, 1952-65 25480791
This page summarizes selected information from the record referenced above and curated into PhosphoSitePlus®, a comprehensive online resource for the study of protein post-translational modifications (NAR, 2015, 43:D512-20). To learn more about the scope of PhosphoSitePlus®, click here.
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S550-p - NHE3 (mouse)
Modsite: AEGERRGsLAFIRSP SwissProt Entrez-Gene
Orthologous residues
NHE3 (human): S555‑p, NHE3 (mouse): S550‑p, NHE3 (rat): S552‑p, NHE3 (rabbit): S554‑p

S603-p - NHE3 (mouse)
Modsite: SLEQRRRsIRDTEDM SwissProt Entrez-Gene
Orthologous residues
NHE3 (human): S607‑p, NHE3 (mouse): S603‑p, NHE3 (rat): S605‑p, NHE3 (rabbit): S607‑p

S554-p - NHE3 (rabbit)
Modsite: TEGERRGsLAFIRSP SwissProt Entrez-Gene
Orthologous residues
NHE3 (human): S555‑p, NHE3 (mouse): S550‑p, NHE3 (rat): S552‑p, NHE3 (rabbit): S554‑p
Characterization
Methods used to characterize site in vivo mutation of modification site, phospho-antibody, western blotting
Disease tissue studied:  colorectal cancer, colorectal carcinoma
Relevant cell lines - cell types - tissues:  C2BBe1 (intestinal), ileum, PS120 (fibroblast)
Cellular systems studied:  cell lines, primary cells
Species studied:  hamster, human, mouse
Enzymes shown to modify site in vitro
Type Enzyme
KINASE PKG2 (human)
Upstream Regulation
Potential in vivo enzymes for site: 
Type Enzyme Evidence Notes
KINASE PKG2 (human) phosphopeptide analysis, transfection of wild-type enzyme, phospho-antibody
Treatments, proteins and their effect on site modification: 
Treatments Referenced Treatments Manipulated Protein Referenced Protein Effect Notes
cAMP_analog increase
H-89 cAMP_analog inhibit treatment-induced increase
NKH_477 increase
H-89 NKH_477 inhibit treatment-induced increase
8pCPT-cGMP increase
H-89 8pCPT-cGMP no effect upon treatment-induced increase
cGMP_analog increase
Downstream Regulation
Effect of modification (function):  activity, inhibited, intracellular localization
Comments:  decreased surface expression of NHE3, phosphorylation of this site with other 2 sites are together necessary for activity inhibition

S607-p - NHE3 (rabbit)
Modsite: SLEQRRRsVRDAEDV SwissProt Entrez-Gene
Orthologous residues
NHE3 (human): S607‑p, NHE3 (mouse): S603‑p, NHE3 (rat): S605‑p, NHE3 (rabbit): S607‑p
Characterization
Methods used to characterize site in vivo mutation of modification site, phospho-antibody, western blotting
Relevant cell lines - cell types - tissues:  ileum, PS120 (fibroblast)
Cellular systems studied:  cell lines, primary cells
Species studied:  hamster, mouse
Enzymes shown to modify site in vitro
Type Enzyme
KINASE PKG2 (human)
Upstream Regulation
Potential in vivo enzymes for site: 
Type Enzyme Evidence Notes
KINASE PKG2 (human) phosphopeptide analysis, transfection of wild-type enzyme, phospho-antibody
Treatments, proteins and their effect on site modification: 
Treatments Referenced Treatments Manipulated Protein Referenced Protein Effect Notes
NKH_477 increase
cGMP_analog increase
Downstream Regulation
Effect of modification (function):  activity, inhibited, intracellular localization
Comments:  decreased surface expression of NHE3, phosphorylation of this site with other 2 sites are together necessary for activity inhibition

S663-p - NHE3 (rabbit)
Modsite: TMRKRLEsFKSAKLG SwissProt Entrez-Gene
Orthologous residues
NHE3 (human): S663‑p, NHE3 (mouse): S659‑p, NHE3 (rat): S661‑p, NHE3 (rabbit): S663‑p
Upstream Regulation
Potential in vivo enzymes for site: 
Type Enzyme Evidence Notes
KINASE PKG2 (human) phosphopeptide analysis, transfection of wild-type enzyme, phospho-antibody
Treatments, proteins and their effect on site modification: 
Treatments Referenced Treatments Manipulated Protein Referenced Protein Effect Notes
cGMP_analog increase
dexamethasone increase
Downstream Regulation
Effect of modification (function):  activity, induced, activity, inhibited, intracellular localization
Comments:  decreased surface expression of NHE3, phosphorylation of this site with other 2 sites are together necessary for activity inhibition, dexamethasone stimulates activity