Baum Matthew L, Kurup Pradeep, Xu Jian, Lombroso Paul J
Child Study Center; New Haven, CT USA.
Commun Integr Biol. 2010 Sep;3(5):419-22. doi: 10.4161/cib.3.5.12692.
STriatal-Enriched Phosphatase (STEP) is a brain-specific protein tyrosine phosphatase that plays a role in synaptic plasticity and has recently been implicated in neurodegenerative disease. STEP opposes the development of synaptic strengthening by dephosphorylating and inactivating key signaling proteins that include the MAP kinases ERK1/2 and p38, as well as the tyrosine kinase Fyn. STEP also dephosphorylates the GluR2 subunit of the AMPAR and the NR2B subunit of the NMDAR, which leads to internalization of the NR1/NR2B and GluR1/GluR2 receptors. STEP levels and activity are regulated through phosphorylation, local translation, ubiquitination and degradation and proteolytic cleavage. Here we review recent progress in understanding the normal regulation of STEP and how this regulation is disrupted in Alzheimer's disease, in which abnormally increased STEP levels and activity contribute to the cognitive deficits.
富含纹状体的磷酸酶（STEP）是一种脑特异性蛋白酪氨酸磷酸酶，在突触可塑性中发挥作用，最近还被认为与神经退行性疾病有关。STEP通过使包括丝裂原活化蛋白激酶ERK1/2和p38以及酪氨酸激酶Fyn在内的关键信号蛋白去磷酸化并使其失活，来对抗突触增强的发展。STEP还使AMPA受体的GluR2亚基和NMDA受体的NR2B亚基去磷酸化，这导致NR1/NR2B和GluR1/GluR2受体的内化。STEP的水平和活性通过磷酸化、局部翻译、泛素化和降解以及蛋白水解切割来调节。在这里，我们综述了在理解STEP正常调节方面的最新进展，以及这种调节在阿尔茨海默病中是如何被破坏的，在阿尔茨海默病中，异常升高的STEP水平和活性导致认知缺陷。
