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Curated Information Page
PubMed Id: 15001544 
Andreozzi F, et al. (2004) Activation of the hexosamine pathway leads to phosphorylation of insulin receptor substrate-1 on Ser307 and Ser612 and impairs the phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin insulin biosynthetic pathway in RIN pancreatic beta-cells. Endocrinology 145, 2845-57 15001544
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, 2012,40:D261-70). To learn more about the scope of PhosphoSitePlus®, click here.
Click on the protein name to open the protein page, and on the RSD number to open the site page.
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S312-p - IRS1 (human)
Orthologous residues
IRS1 (human): S312‑p, IRS1 (mouse): S307‑p, IRS1 (rat): S307‑p
Characterization
 Methods used to characterize site in vivo phospho-antibody, western blotting
 Relevant cell lines - cell types - tissues:  RIN (epithelial)
 Cellular systems studied:  cell lines
 Species studied:  rat
Upstream Regulation
 Potential in vivo enzymes for site: 
Type Enzyme Evidence Notes
KINASE JNK1 (human) pharmacological inhibitor of upstream enzyme
 Treatments, proteins and their effect on site modification: 
Treatments Referenced Treatments Manipulated Protein Referenced Protein Effect Notes
glucose increase High glucose concentrations (25 mM)
azaserine glucose inhibit treatment-induced increase High glucose concentrations (25 mM)
glucosamine increase
JNK inhibitor I glucosamine inhibit treatment-induced increase

Y612-p - IRS1 (human)
Orthologous residues
IRS1 (human): Y612‑p, IRS1 (mouse): Y608‑p, IRS1 (rat): Y608‑p
Characterization
 Methods used to characterize site in vivo phospho-antibody, western blotting
 Relevant cell lines - cell types - tissues:  RIN (epithelial)
 Cellular systems studied:  cell lines
 Species studied:  rat
Upstream Regulation
 Treatments, proteins and their effect on site modification: 
Treatments Referenced Treatments Manipulated Protein Referenced Protein Effect Notes
insulin increase
glucosamine insulin inhibit treatment-induced increase
glucose insulin augment treatment-induced increase High glucose concentrations (25 mM)

S616-p - IRS1 (human)
Orthologous residues
IRS1 (human): S616‑p, IRS1 (mouse): S612‑p, IRS1 (rat): S612‑p
Characterization
 Methods used to characterize site in vivo phospho-antibody, western blotting
 Relevant cell lines - cell types - tissues:  RIN (epithelial)
 Cellular systems studied:  cell lines
 Species studied:  rat
Upstream Regulation
 Potential in vivo enzymes for site: 
Type Enzyme Evidence Notes
KINASE ERK1 (human) pharmacological inhibitor of upstream enzyme
 Treatments, proteins and their effect on site modification: 
Treatments Referenced Treatments Manipulated Protein Referenced Protein Effect Notes
glucose increase High glucose concentrations (25 mM)
azaserine glucose inhibit treatment-induced increase
glucosamine increase
PD98059 glucosamine inhibit treatment-induced increase

Y632-p - IRS1 (human)
Orthologous residues
IRS1 (human): Y632‑p, IRS1 (mouse): Y628‑p, IRS1 (rat): Y628‑p
Characterization
 Methods used to characterize site in vivo phospho-antibody, western blotting
 Relevant cell lines - cell types - tissues:  RIN (epithelial)
 Cellular systems studied:  cell lines
 Species studied:  rat
Upstream Regulation
 Treatments, proteins and their effect on site modification: 
Treatments Referenced Treatments Manipulated Protein Referenced Protein Effect Notes
insulin increase
glucosamine insulin inhibit treatment-induced increase
glucose insulin augment treatment-induced increase High glucose concentrations (25 mM)

S473-p - Akt1 (rat)
Orthologous residues
Akt1 (human): S473‑p, Akt1 (mouse): S473‑p, Akt1 (rat): S473‑p, Akt1 (fruit fly): S586‑p, Akt1 (cow): S473‑p
Characterization
 Methods used to characterize site in vivo phospho-antibody, western blotting
 Relevant cell lines - cell types - tissues:  RIN (epithelial)
 Cellular systems studied:  cell lines
 Species studied:  rat
Upstream Regulation
 Treatments, proteins and their effect on site modification: 
Treatments Referenced Treatments Manipulated Protein Referenced Protein Effect Notes
insulin increase
glucosamine insulin inhibit treatment-induced increase

T203-p - ERK1 (rat)
Orthologous residues
ERK1 (human): T202‑p, ERK1 iso2 (human): T202‑p, ERK1 iso3 (human): T202‑p, ERK1 (mouse): T203‑p, ERK1 (rat): T203‑p, ERK1 (hamster): T192‑p
Characterization
 Methods used to characterize site in vivo phospho-antibody, western blotting
 Relevant cell lines - cell types - tissues:  RIN (epithelial)
 Cellular systems studied:  cell lines
 Species studied:  rat
Upstream Regulation
 Treatments, proteins and their effect on site modification: 
Treatments Referenced Treatments Manipulated Protein Referenced Protein Effect Notes
glucose increase High glucose concentrations (25 mM)
azaserine glucose inhibit treatment-induced increase
glucosamine glucose augment treatment-induced increase
JNK inhibitor I glucosamine inhibit treatment-induced increase

Y205-p - ERK1 (rat)
Orthologous residues
ERK1 (human): Y204‑p, ERK1 iso2 (human): Y204‑p, ERK1 iso3 (human): Y204‑p, ERK1 (mouse): Y205‑p, ERK1 (rat): Y205‑p, ERK1 (hamster): Y194‑p
Characterization
 Methods used to characterize site in vivo phospho-antibody, western blotting
 Relevant cell lines - cell types - tissues:  RIN (epithelial)
 Cellular systems studied:  cell lines
 Species studied:  rat
Upstream Regulation
 Treatments, proteins and their effect on site modification: 
Treatments Referenced Treatments Manipulated Protein Referenced Protein Effect Notes
glucose increase High glucose concentrations (25 mM)
azaserine glucose inhibit treatment-induced increase
glucosamine glucose augment treatment-induced increase
JNK inhibitor I glucosamine inhibit treatment-induced increase

T183-p - ERK2 (rat)
Orthologous residues
ERK2 (human): T185‑p, ERK2 (mouse): T183‑p, ERK2 (rat): T183‑p, ERK2 (chicken): T193‑p
Characterization
 Methods used to characterize site in vivo phospho-antibody, western blotting
 Relevant cell lines - cell types - tissues:  RIN (epithelial)
 Cellular systems studied:  cell lines
 Species studied:  rat
Upstream Regulation
 Treatments, proteins and their effect on site modification: 
Treatments Referenced Treatments Manipulated Protein Referenced Protein Effect Notes
glucose increase High glucose concentrations (25 mM)
azaserine glucose inhibit treatment-induced increase
glucosamine glucose augment treatment-induced increase
JNK inhibitor I glucosamine inhibit treatment-induced increase

Y185-p - ERK2 (rat)
Orthologous residues
ERK2 (human): Y187‑p, ERK2 (mouse): Y185‑p, ERK2 (rat): Y185‑p, ERK2 (chicken): Y195‑p
Characterization
 Methods used to characterize site in vivo phospho-antibody, western blotting
 Relevant cell lines - cell types - tissues:  RIN (epithelial)
 Cellular systems studied:  cell lines
 Species studied:  rat
Upstream Regulation
 Treatments, proteins and their effect on site modification: 
Treatments Referenced Treatments Manipulated Protein Referenced Protein Effect Notes
glucose increase High glucose concentrations (25 mM)
azaserine glucose inhibit treatment-induced increase
glucosamine glucose augment treatment-induced increase
JNK inhibitor I glucosamine inhibit treatment-induced increase

T183-p - JNK1 (rat)
Orthologous residues
JNK1 (human): T183‑p, JNK1 iso2 (human): T183‑p, JNK1 iso3 (human): T183‑p, JNK1 (mouse): T183‑p, JNK1 (rat): T183‑p
Characterization
 Methods used to characterize site in vivo phospho-antibody, western blotting
 Relevant cell lines - cell types - tissues:  RIN (epithelial)
 Cellular systems studied:  cell lines
 Species studied:  rat
Upstream Regulation
 Treatments, proteins and their effect on site modification: 
Treatments Referenced Treatments Manipulated Protein Referenced Protein Effect Notes
glucose increase High glucose concentrations (25 mM)
azaserine glucose inhibit treatment-induced increase
glucosamine glucose augment treatment-induced increase
JNK inhibitor I glucosamine inhibit treatment-induced increase

Y185-p - JNK1 (rat)
Orthologous residues
JNK1 (human): Y185‑p, JNK1 iso2 (human): Y185‑p, JNK1 iso3 (human): Y185‑p, JNK1 (mouse): Y185‑p, JNK1 (rat): Y185‑p
Characterization
 Methods used to characterize site in vivo phospho-antibody, western blotting
 Relevant cell lines - cell types - tissues:  RIN (epithelial)
 Cellular systems studied:  cell lines
 Species studied:  rat
Upstream Regulation
 Treatments, proteins and their effect on site modification: 
Treatments Referenced Treatments Manipulated Protein Referenced Protein Effect Notes
glucose increase High glucose concentrations (25 mM)
azaserine glucose inhibit treatment-induced increase
glucosamine glucose augment treatment-induced increase
JNK inhibitor I glucosamine inhibit treatment-induced increase

T183-p - JNK2 (rat)
Orthologous residues
JNK2 (human): T183‑p, JNK2 iso2 (human): T183‑p, JNK2 iso3 (human): T183‑p, JNK2 (mouse): T183‑p, JNK2 (rat): T183‑p
Characterization
 Methods used to characterize site in vivo phospho-antibody, western blotting
 Relevant cell lines - cell types - tissues:  RIN (epithelial)
 Cellular systems studied:  cell lines
 Species studied:  rat
Upstream Regulation
 Treatments, proteins and their effect on site modification: 
Treatments Referenced Treatments Manipulated Protein Referenced Protein Effect Notes
glucose increase High glucose concentrations (25 mM)
azaserine glucose inhibit treatment-induced increase
glucosamine glucose augment treatment-induced increase
JNK inhibitor I glucosamine inhibit treatment-induced increase

Y185-p - JNK2 (rat)
Orthologous residues
JNK2 (human): Y185‑p, JNK2 iso2 (human): Y185‑p, JNK2 iso3 (human): Y185‑p, JNK2 (mouse): Y185‑p, JNK2 (rat): Y185‑p
Characterization
 Methods used to characterize site in vivo phospho-antibody, western blotting
 Relevant cell lines - cell types - tissues:  RIN (epithelial)
 Cellular systems studied:  cell lines
 Species studied:  rat
Upstream Regulation
 Treatments, proteins and their effect on site modification: 
Treatments Referenced Treatments Manipulated Protein Referenced Protein Effect Notes
glucose increase High glucose concentrations (25 mM)
azaserine glucose inhibit treatment-induced increase
glucosamine glucose augment treatment-induced increase
JNK inhibitor I glucosamine inhibit treatment-induced increase

S63-p - Jun (rat)
Orthologous residues
Jun (human): S63‑p, Jun (mouse): S63‑p, Jun (rat): S63‑p
Characterization
 Methods used to characterize site in vivo phospho-antibody, western blotting
 Relevant cell lines - cell types - tissues:  RIN (epithelial)
 Cellular systems studied:  cell lines
 Species studied:  rat
Upstream Regulation
 Treatments, proteins and their effect on site modification: 
Treatments Referenced Treatments Manipulated Protein Referenced Protein Effect Notes
glucose increase High glucose concentrations (25 mM)
azaserine glucose inhibit treatment-induced increase
glucosamine glucose augment treatment-induced increase
JNK inhibitor I glucosamine inhibit treatment-induced increase

S2448-p - mTOR (rat)
Orthologous residues
mTOR (human): S2448‑p, mTOR (mouse): S2448‑p, mTOR (rat): S2448‑p
Characterization
 Methods used to characterize site in vivo phospho-antibody, western blotting
 Relevant cell lines - cell types - tissues:  RIN (epithelial)
 Cellular systems studied:  cell lines
 Species studied:  rat
Upstream Regulation
 Treatments, proteins and their effect on site modification: 
Treatments Referenced Treatments Manipulated Protein Referenced Protein Effect Notes
insulin increase
glucosamine insulin inhibit treatment-induced increase

T412-p - p70S6K (rat)
Orthologous residues
p70S6K (human): T412‑p, p70S6K iso2 (human): T389‑p, p70S6K (mouse): T412‑p, p70S6K (rat): T412‑p, p70S6K iso2 (rat): T389‑p, p70S6K (fruit fly): T398‑p
Characterization
 Methods used to characterize site in vivo phospho-antibody, western blotting
 Relevant cell lines - cell types - tissues:  RIN (epithelial)
 Cellular systems studied:  cell lines
 Species studied:  rat
Upstream Regulation
 Treatments, proteins and their effect on site modification: 
Treatments Referenced Treatments Manipulated Protein Referenced Protein Effect Notes
insulin increase
glucosamine insulin inhibit treatment-induced increase

T1466-p - TSC2 (rat)
Orthologous residues
TSC2 (human): T1462‑p, TSC2 iso3 (human): T1418‑p, TSC2 iso4 (human): T1439‑p, TSC2 (mouse): T1465‑p, TSC2 iso6 (mouse): T1443‑p, TSC2 (rat): T1466‑p, TSC2 iso2 (rat): T1423‑p
Characterization
 Methods used to characterize site in vivo phospho-antibody, western blotting
 Relevant cell lines - cell types - tissues:  RIN (epithelial)
 Cellular systems studied:  cell lines
 Species studied:  rat
Upstream Regulation
 Treatments, proteins and their effect on site modification: 
Treatments Referenced Treatments Manipulated Protein Referenced Protein Effect Notes
insulin increase
glucosamine insulin inhibit treatment-induced increase


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