Cloning and Characterization of a Lymphoid-Specific, Inducible Human Protein Tyrosine Phosphatase, Lyp

Abstract

Protein tyrosine phosphatases act in conjunction with protein kinases to regulate the tyrosine phosphorylation events that control cell activation and differentiation. 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 and an NXXY motif that, if phosphorylated, may be recognized by phosphotyrosine binding (PTB) domains. Comparison of the Lyp amino acid sequence with other known proteins shows 70% identity with the murine phosphatase PEP. The human Lyp gene was localized to chromosome 1p13 by fluorescence in situ hybridization analysis. We also identified an alternative spliced form of Lyp RNA, Lyp2. This isoform encodes a smaller 85-kD protein with an alternative C-terminus. 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. Increased Lyp1 expression can be induced by activation of resting peripheral T lymphocytes with phytohemagglutinin or anti-CD3. Lyp1 was found to be constitutively associated with the proto-oncogene c-Cbl in thymocytes and T cells. Overexpression of lyp1 reduces Cbl tyrosine phosphorylation, suggesting that it may be a substrate of the phosphatase. Thus, Lyp may play a role in regulating the function of Cbl and its associated protein kinases.

CD45, CD148, and Lyp/Pep: critical phosphatases regulating Src family kinase signaling networks in immune cells

“…Lyp ⁄ Pep is a hematopoietic tyrosine phosphatase that contains an N-terminal phosphatase domain and four proline-rich domains, the most C-terminal of which lies within a 20 amino acid conserved region that defines a small family of phosphatases, the so-called PEST group (3,152,153) (Fig. 2).…”

“…The function of this conserved C-terminal domain remains unclear. Pep and Lyp are species orthologs but vary considerably in their C-terminal halves (153). There is 89% sequence homology between the phosphatase domains, but only 61% homology for the remaining portions of the proteins.…”

Current immunogenetic predisposition to tuberculosis in the Moroccan population

“…The PTPN22 gene is located at the chromosomal region 1p13.3-p13.1 and encodes the protein belonging the nonreceptor class 4 subfamily of the protein tyrosine phosphatase family. This protein is the intracellular lymphoid tyrosine phosphatase (LYP) (Cohen, Dadi, Shaoul, Sharfe, & Roifman, 1999) and it is only expressed in the immune cells, including dendritic and B cells, and particularly in T cells (Rhee & Veillette, 2012).…”

PEST family phosphatases in immunity, autoimmunity, and autoinflammatory disorders

“…PTP-HSCF appears to be primarily expressed in primitive hematopoietic cells, although it may also be present in other cell types (1)(2)(3)(4)(5)(6)(7)(8). All PEST family members reside in the cytoplasm, although some data suggested that a fraction of PEP may be found in the nucleus (10).…”

“…It is unclear whether a similar interaction also exists between LYP and Csk in normal human T cells. PEP ⁄ LYP also binds to Grb2 and c-Cbl (2,18). In contrast, PTP-PEST prominently associates with proteins involved in the organization of the cytoskeleton (13,16,(19)(20)(21)(22)(23)(23)(24)(25)(26)(27).…”