"We have isolated a previously undescribed human phosphatase, Lyp, that encodes an intracellular 105-kD protein containing a single tyrosine phosphatase catalytic domain. The noncatalytic domain contains four proline-rich potential SH3 domain binding sites"

"Lyp1 was found to be constitutively associated with the proto-oncogene c-Cbl in thymocytes and T cells."

"The lyp phosphatases are predominantly expressed in lymphoid tissues and cells, with Lyp1 being highly expressed in thymocytes and both mature B and T cells."

"Most were found in the cytosol and many were enriched at the plasma membrane."

"15 of the currently known 24 intracellular PTPases are expressed in T cells"

"We report that 15 of the currently known 24 intracellular PTPases are expressed in T cells"

"Several potential substrates were identified in lysates from pervanadate-stimulated Jurkat cells using PTPN22-D195A/C227S, an optimized substrate trap mutant of PTPN22."

"Native PTPN22 dephosphorylated Lck and Zap70 at their activating tyrosine residues Tyr-394 and Tyr-493, respectively"

"but not at the regulatory tyrosines Tyr-505 (Lck) or Tyr-319 (Zap70)"

"we report the identification of a bidentate salicylic acid-based Lyp inhibitor I-C11 with excellent cellular efficacy"

"We show that Lyp is phosphorylated exclusively at Ser-35 by PKC both in vitro and in vivo."

"Ser-35 phosphorylation impairs Lyp's ability to inactivate the Src family kinases and down-regulate T cell receptor signaling."

"The LYP 620Trp variant is associated with reduced activation, proliferation and IL-2 production in CD4(+)T cells among T1D patients."

"a profoundly decreased intracellular calcium flux in CD4(+)T cells after PHA stimulus was detected among 620Trp carriers"

"B cell signal transduction is impaired in individuals who express the variant."

"This defect in signaling is characterized by a deficit in proliferation, a decrease in phosphorylation of key signaling proteins"

"and is reversed by inhibition of Lyp"

"The tyrosine phosphatase LYP, which down-regulates LCK activity in T cell response"

"LYP R620W may be a gain of function mutation which suppresses TCR signaling."

"The CT genotype of the rs2476601 SNP was significantly (P = 0.0013) associated with reduced NK cell CD3(-) CD56(+) fraction in culture."

"the PTPN22 gene might have an important immune regulatory role in NK cell function which needs further investigation"

"Ptpn22 selectively regulated type 1 IFN production after TLR engagement in myeloid cells."

"PTPN22 directly associated with TNF receptor-associated factor 3 (TRAF3) and promotes TRAF3 lysine 63-linked ubiquitination."

"The disease-associated PTPN22W variant failed to promote TRAF3 ubiquitination, type 1 IFN upregulation"

"Ptpn22 promoted host antiviral responses and was critical for TLR agonist-induced, type 1 IFN-dependent suppression of inflammation in colitis and arthritis"

"MDP-treatment induced PTPN22 expression and activity in human and mouse cells."

"Loss of PTPN22 enhanced basal and MDP-induced phosphorylation of p38 and MDP-induced JNK phosphorylation."

"PTPN22 deficiency finally resulted in enhanced secretion of the pro-inflammatory cytokines IL-6, IL-8 and TNF in human THP-1 monocytes"

"Additionally, loss of PTPN22 resulted in increased, MDP-mediated autophagy in human and mouse cells."

"PTPN22 controls NOD2 signaling, and loss of PTPN22 renders monocytes more reactive towards bacterial products"

"dephosphorylates NLRP3 upon inflammasome induction, allowing efficient NLRP3 activation and subsequent IL-1β release"

"protein tyrosine phosphatase non-receptor 22 (PTPN22), variants in which are associated with chronic inflammatory disorders, dephosphorylates NLRP3 upon inflammasome induction"

"PTPN22 deficiency resulted in pronounced colitis, increased NLRP3 phosphorylation, but reduced levels of mature IL-1β"