Cited by 185Protein Tyrosine PhosphatasesProtein Kinase Regulation and GTPase SignalingNeuroscience and Neuropharmacology Research

Striatal enriched phosphatase 61 dephosphorylates Fyn at phosphotyrosine 420

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Nguyen, Tri-Hung, Liu, Jian, Lombroso, Paul J.·2002·Journal of Biological Chemistry

Abstract

A family of protein tyrosine phosphatases enriched within the central nervous system called striatal enriched phosphatase (STEP) has been implicated in the regulation of the N-methyl-d-aspartate receptor. STEP(61), a membrane-associated isoform located in the postsynaptic densities (PSDs) of striatal neurons, contains two transmembrane domains, two proline-rich domains, and a kinase-interacting motif. This study demonstrates that STEP(61) associates with Fyn, a member of the Src family kinases that is also enriched in PSDs. By using human embryonic kidney 293 cells for co-transfection, we determined that a substrate-trapping variant (STEP(61) CS) binds to Fyn but not to other members of the Src family present in PSDs. In a complementary experiment, myc-tagged Fyn immunoprecipitates STEP(61) CS. STEP(61) binds to Fyn through one of its proline-rich domains and the kinase-interacting motif domain, whereas Fyn binds to STEP(61) through its Src homology 2 domain and the unique N-terminal domain. STEP(61) CS pulls down Fyn when the Tyr(420) site is phosphorylated. In vitro, wild-type STEP(61) dephosphorylates Fyn at Tyr(420) but not at Tyr(531). These results suggest that STEP regulates the activity of Fyn by specifically dephosphorylating the regulatory Tyr(420) and may be one mechanism by which Fyn activity is decreased within PSDs.

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Crossref · 10.1074/jbc.m111683200

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  • STEP dephosphorylates and deactivates Fyn, enhancing the overall effect of STEP on NMDAR endocytosis.

    “STEP additionally dephosphorylates and deactivates Fyn, enhancing the overall effect of STEP on NMDAR endocytosis [36].”

    From ApoE, ApoE Receptors, and the Synapse in Alzheimer's Disease (2017) · cites this paper as [36]

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Authors
Nguyen, T.-H., Liu, J., & Lombroso, P. J.
Affiliations
Yale University (US)
Corresponding author
Nguyen, Tri-Hung
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2002-07
Volume
277
Issue
27
Pages
24274-24279
ISSN
0021-9258 (ISSN-L)
OpenAlex
W2154343843
Cited by
185
References
36
Citations by year
2026: 4 · 2025: 2 · 2024: 7 · 2023: 5 · 2022: 3 · 2021: 7 · 2020: 7 · 2019: 3 · 2018: 5 · 2017: 15 · 2016: 13 · 2015: 9 · 2014: 12 · 2013: 8 · 2012: 31
FWCI
1.04
Type
journal article
Language
en
Open access
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
National Institute of Mental Health (MH 18268, KO2 MH01527, R01MH052711, K02MH001527, R01 MH52711, T32MH018268)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
Fyn, protein tyrosine phosphatase, dephosphorylation, Src family kinases, postsynaptic density, striatum, proline-rich region, SH2 domain, substrate specificity
MeSH terms
Animals, Corpus Striatum, Female, Neurons, Protein-Tyrosine Kinases, Proto-Oncogene Proteins, Protein Tyrosine Phosphatases, Phosphotyrosine, Rats, Long-Evans, Proto-Oncogene Proteins c-fyn, Rats, Protein Tyrosine Phosphatases, Non-Receptor

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