| Striatal enriched phosphatase (STEP, also known as PTPN5), is a protein tyrosine phosphatase expressed in dopaminoceptive neurons of the central nervous system. Alternative splicing produces the cytosolic STEP46 and the membrane-associated STEP61 isoforms of STEP. Dopamine activates D1 receptors and PKA, which in turn phosphorylate both isoforms of STEP. Phosphorylation of STEP61 occurs at Ser160 and Ser221, while STEP46 is phosphorylated at Ser49 (equivalent to Ser221 of STEP61). NMDA-mediated activation of STEP is an important mechanism for regulation of Erk activity in neurons. Furthermore, STEP is involved in the regulation of both NMDAR and AMPAR trafficking. Due to its importance in cognitive function, STEP may play a role in Alzheimer's disease. |
