Ask about this productRelated genes to: PTPN5 Blocking Peptide
- Gene:
- PTPN5 NIH gene
- Name:
- protein tyrosine phosphatase non-receptor type 5
- Previous symbol:
- -
- Synonyms:
- STEP, PTPSTEP, STEP61
- Chromosome:
- 11p15.1
- Locus Type:
- gene with protein product
- Date approved:
- 1992-02-12
- Date modifiied:
- 2019-02-14
Related products to: PTPN5 Blocking Peptide
Related articles to: PTPN5 Blocking Peptide
- Striatal-Enriched Protein Tyrosine Phosphatase (STEP) constrains synaptic potentiation by dephosphorylating postsynaptic substrates, but its presynaptic role has remained unclear. Here, we identify a previously unrecognized function of STEP in regulating axonal differentiation and synapse assembly. Genetic and pharmacological manipulation of STEP in vivo and in vitro show that STEP limits presynaptic maturation by restricting synaptic vesicle protein clustering along developing hippocampal axons. Using a reconstituted circuit-on-a-chip we show that loss of presynaptic STEP is sufficient to significantly increase the number of axodendritic synapses. Functional imaging further revealed that the increased synaptic puncta observed in STEP KO neurons actively undergo depolarization-evoked vesicle exocytosis, representing bona fide functional synapses. Multielectrode array recordings reveal that STEP deletion increases neuronal excitability, and network synchrony, hallmarks of enhanced presynaptic efficacy. Mechanistically, these effects reflect sustained phosphorylation of STEP promoting presynaptic assembly and release competence. Importantly, inhibiting STEP also rescues presynaptic differentiation defects in KO neurons, implicating aberrant STEP signaling in Fragile X-associated synaptic pathology. Thus, STEP serves as a phosphatase gatekeeper that restrains presynaptic differentiation and neurotransmission, and its inhibition may offer a therapeutic strategy to correct synaptic deficits in Fragile X Syndrome. - Source: PubMed
Publication date: 2026/06/10
Pires Joel PTomé DiogoMele MirandaCaulino-Rocha AnaCorti ElisaMilosevic IraBaltazar Graça FAlmeida Ramiro D - Organophosphate flame retardants (OPFRs) are ubiquitous flame-retardant additives with endocrine-disrupting properties. Despite increasing evidence that OPFRs affect neurodevelopment, their effects on the neuroendocrine stress response remain poorly understood. To examine their long-term effect on stress regulation, we treated pregnant C57Bl/6J dams to a mixture of tris(1,3-dichloro-2-propyl) phosphate (TDCPP), triphenyl phosphate (TPP), and tricresyl phosphate (TCP; 1 mg/kg each) from gestational day (GD) 7 through postnatal day (PND) 14. Adult offspring (age 8-9 weeks) were then challenged with acute stressors, including 1-hour restraint or a 6-day acute variable stress (AVS) paradigm. Perinatal OPFR exposure produced persistent, sex-specific alterations in the hypothalamic-pituitary-adrenal (HPA) axis and stress-related neurocircuitry. Following 1-hour restraint, OPFR-treated females showed heightened serum corticosterone. In addition, gene expression analysis revealed sex-dependent disruptions in key stress-regulatory pathways after OPFR treatment and 1-hour restraint in the hypothalamus (Crhr1, Crhr2, Ptpn5) and pituitary (Crhr1, Pomc, Nr3c1). Females demonstrated more differences in adrenal gene expression related to steroidogenesis (Mc2r, Cyp11b2) and catecholamine biosynthesis (Dbh, Pnmt), with OPFR-treated groups having blunted responses. OPFR AVS females displayed reduced corticosterone and Crh messenger RNA in the hypothalamus, and downregulated Pacap/Pac1r expression in the bed nucleus of the stria terminalis (BNST), accompanied by increased behavioral avoidance and immobility. In males, OPFR exposure led to increased BNST Pacap and Pac1r expression, along with hyperactivity and avoidance behaviors. Together, these findings demonstrate that early-life OPFR exposure induces lasting, sex-specific dysregulation of the HPA axis and associated stress circuits, highlighting OPFRs as developmental neuroendocrine disruptors with implications for mood- and stress-related disorders. - Source: PubMed
Rojas Catherine MDeLucca JuliaBrown Caylee AYasrebi AliChiou SavannahBello Nicholas TRoepke Troy A - Cognitive impairment in schizophrenia remains insufficiently addressed by existing treatments. Current FDA-approved therapies primarily modulate neurotransmitter systems, resulting in incomplete symptom control and substantial adverse effects. There is therefore a critical need for therapeutic strategies that more directly address the intracellular signaling mechanisms underlying synaptic dysfunction and cognitive deficits in schizophrenia. Protein phosphatases represent an essential but historically underexplored class of signaling enzymes that regulate phosphorylation-dependent control of synaptic receptor trafficking, plasticity, and neuronal circuit function. Although multiple phosphatases have been implicated in schizophrenia through genetic, post-mortem, and functional studies, their therapeutic targeting has been limited by challenges related to selectivity, cellular permeability, and pleiotropy. Here, we review the etiology of schizophrenia and limitations of current pharmacological approaches, synthesize evidence linking specific protein phosphatases to schizophrenia pathophysiology, and discuss emerging strategies, including allosteric modulation and targeted protein degradation, that may enable selective intervention in phosphatase-driven signaling pathways. We highlight the striatal-enriched tyrosine phosphatase STEP () as a case study illustrating how selective phosphatase modulation can restore synaptic signaling in schizophrenia-relevant models. - Source: PubMed
Publication date: 2026/03/20
Molony Lauren ETautz Lutz - This article provides a comprehensive review of the molecular and neurodevelopmental mechanisms underlying schizophrenia, with a particular focus on the roles of protein tyrosine phosphatases (PTPs). Schizophrenia is a neurodevelopmental disorder with a complex etiology involving genetic and environmental factors and characterized by diverse clinical symptoms. The review synthesizes recent advances in understanding how dysregulation of specific PTPs, including PTP1B, PTP receptor gamma (PTPRG), PTPN5 (encoding striatal-enriched PTP [STEP]), and PTP receptor type A (PTPRA), contributes to disrupted synaptic signaling, neurotransmitter dysfunction, and neurodevelopmental abnormalities observed in schizophrenia. Key findings include evidence that altered phosphorylation states, impaired myelination, and aberrant modulation of N-methyl-D-aspartate (NMDA) and dopamine receptor function are central to disease pathophysiology. The review also examines the therapeutic potential of targeting PTP1B and other phosphatases, highlighting promising animal model data while emphasizing the need for additional clinical research. Collectively, the article underscores the importance of phosphatase signaling pathways in the pathogenesis and potential treatment of schizophrenia. - Source: PubMed
Publication date: 2026/01/27
Murugesan KarthikaRebellow DelvyKasagga AlousiousMon Aye MAnwar Summayya - Mental disorders are a severe problem of modern society. Significant in these conditions are the striatal-enriched protein tyrosine phosphatase (STEP) ( gene) and the serotonergic system. Nevertheless, the association between them is poorly studied. The aim of this research was to investigate the effects of gene knockout on behavior and the serotonin system in mice. - Source: PubMed
Publication date: 2026/01/14
Moskaliuk VitaliiKomleva PolinaKhotskin NikitaArefieva AllaShevelev OlegKorablev AlexeySerova IrinaBattulin NarimanKulikov AlexanderNaumenko VladimirBazovkina DaryaKulikova Elizabeth