PTPN5: Human striatal enriched protein tyrosine phosphatase (STEP)
PDB Code: 2BIJ
STEP, a striatal-enriched protein tyrosine phosphatase, is preferentially expressed in neurons of the basal ganglia, hippocampus, cortex and related structures. Alternative splicing produces various STEP family members, and both cytosolic (STEP 46) and membrane-associated (STEP 61) variants exist.
STEP and its non-neuronal homologs like He-PTP have been implicated in the regulation of ERK activity. Both splice products STEP 61 and STEP 46 are phosphorylated in a common kinase-interacting domain (KIM) that binds to ERK2. The kinase PKA phosphorylates STEP 46 at Ser49 (equivalent to Ser221 in STEP 61) which decreases the activity of STEP by reducing its affinity for its substrates. Dephosphorylated STEP binds and inactivates ERK through dephosphorylation of the tyrosine residue in its activation domain and blocks nuclear translocation of the kinase. These findings establish STEP as an important tyrosine phosphatase involved in regulating the duration of ERK signaling in neurons.

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