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Blood, Vol. 93 No. 6 (March 15), 1999:
pp. 2013-2024
Cloning and Characterization of a Lymphoid-Specific, Inducible
Human Protein Tyrosine Phosphatase, Lyp
Shai Cohen,
Harjit Dadi,
Ester Shaoul,
Nigel Sharfe, and
Chaim M. Roifman
From the Division of Immunology and Allergy, Department of
Paediatrics, Infection, Immunity, Injury and Repair Programme, Research
Institute, The Hospital for Sick Children and the University of
Toronto, Toronto, Ontario, Canada.
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.
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