STEP

2022-05-20: reference:

Striatal-Enriched protein tyrosine phosphatase (STEP)/Protein tyrosine phosphatase (PTPN5) #

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  • KIM = kinase interacting motif. Clearly not since there are other sites
  • Inhibited by Protein Kinase A (one source could be mGluR II/III): Ser221 & Ser49 on STEP 61 and STEP 46, respectively. Also Ser160 on STEP61.
  • Cys65 andCys 76 in TM region promote dimerization of STEP and reduce its phosphatase activity 93 .
  • Activated by PP1, PP2B.
  • Cleaved, deactivated, by Calpain.
• KO increases dominance behavior

Targets #

Normally promotes exocytosis of NMDAR via inhibiting (phosphorylating) Fyn, and by dephosphorylating NR2B @ Tyr1472 and NR2A.

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  • Dephosphorylates: p38 (activates), Fyn (deactivates), ERK (by means of inhibiting PHLPP1β), NR2B @ Tyr1472, NR2A (I think this inhibits endocytosis), as well as Pyk2.
  • Yeah this is a PDZ: STEP 61 binds to PSD-95, and this promotes ubiquination. Maybe this is just its default fate instead of proteolysis via calpain or other stuff. Therefore it mediates endocytosis of NR2B on numerous fronts.
    • NMDAR-activated p38 death pathway is disrupted by a peptide (Tat-NR2B9c) that uncouples GluN2B from PSD-95. R Elevated expression is seen in Alzheimer’s. Decreased levels in cerebral ischemia, Huntington’s.