Cloning and characterization of a lymphoid-specific, inducible human protein tyrosine phosphatase, Lyp

Protein tyrosine phosphatases act in conjunction with protein kinases to re gulate the tyrosine phosphorylation events that control cell activation and differentiation. We have isolated a previously undescribed human phosphata se. Lyp, that encodes an intracellular 105-kD protein containing a single t yrosine 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 local ized 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 pho sphatases are predominantly expressed in lymphoid tissues and cells, with L yp1 being highly expressed in thymocytes and both mature B and T cells. Inc reased Lyp1 expression can be induced by activation of resting peripheral T lymphocytes with phytohemagglutinin or anti-CD3. Lyp1 was found to be cons titutively associated with the proto-oncogene c-Cbl in thymocytes and T cel ls. Overexpression of lyp1 reduces Cbl tyrosine phosphorylation, suggesting that it may be a substrate of the phosphatase. Thus, Lyp may play a role i n regulating the function of Cbl and its associated protein kinases. (C) 19 99 by The American Society of Hematology.