Protein tyrosine phosphatase non-receptor type 1 (PTP1B) (PTPN1)

Protein tyrosine phosphatase non-receptor type 1 (PTPN1) mRNA encodes the PTP1B enzyme, a critical negative regulator of both insulin and leptin signaling pathways [1, 2]. PTP1B functions by dephosphorylating the activated insulin receptor and insulin receptor substrates (IRS-1/2), thereby terminating the insulin signal and contributing to insulin resistance [3]. It similarly regulates leptin signaling through the dephosphorylation of JAK2, making it a significant target for the treatment of type 2 diabetes and obesity [2, 4]. Beyond its metabolic roles, PTP1B is implicated in the progression of various cancers, including breast and colorectal cancer, where it can act as an oncogene by modulating Src and MAPK signaling [5]. While the development of small-molecule inhibitors has been hindered by the highly polar nature of the catalytic site and high homology with other phosphatases like TCPTP, targeting PTPN1 at the mRNA level offers a promising alternative [3, 4]. Antisense oligonucleotides (ASOs), such as IONIS-PTP1BRx, are designed to bind to PTPN1 mRNA and trigger its degradation, effectively reducing PTP1B protein expression and improving metabolic parameters in clinical models [4]. Sources: [1] UniProt P18031; [2] NCBI Gene 5770; [3] Tonks (2003) FEBS Lett; [4] Ionis Pharmaceuticals; [5] Krishnan et al. (2018) Nat Rev Cancer.

Other names

PTP1BProtein-tyrosine phosphatase 1BPTP-1BTyrosine-protein phosphatase non-receptor type 1

Antisense oligonucleotide-mediated mRNA degradation; Small molecule inhibition of the PTP1B catalytic or allosteric sites.