PTPN7: Human hematopoietic protein tyrosine phosphatase (HEPTP)
PDB Code: 2A3K
PTPN7 (also named leukocyte PTP (LPTP) and hematopoetic PTP (HEPTP)) is a member of the protein tyrosine phosphatase (PTP) family. It is preferentially expressed in a variety of hematopoietic cells, particularly B and T lymphocytes, and is an early response gene in lymphokine stimulated cells. PTPN7 belongs to a subgroup of PTPs with two other members (PTPN5 and PTPRR) which have a non-catalytic N-terminal kinase interaction motif (KIM). These phosphatases interact with and negatively regulate mitogen-activated protein kinases ERK1/2 and p38 by dephosphorylation of the critical phospho-tyrosine in the activation loop of ERK. It has been suggested that PTPN7 plays a negative role in T cell antigen receptor (TCR) signaling by down regulating MAP kinases activity in the cytosol at early time points of T cell activation. This data have been confirmed by PTPN7?/? mice which show an elevated activation of Erk signalling after exposure to protein kinase C activator (PMA) and TCR stimulation. Amplification and overexpression of PTPN7 has been suggested to be an important cofactor contributing to abnormal myeloid cell growth. In addition, PTPN7 gene maps to region 1q32.1 where chromosomal deletions are observed in non-Hodgkin lymphomas. We determined the structure of PTPN7 phosphatase domain which contains also part of the N-terminal kinase interaction motif at 2.6 Å resolution.
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