Research for a protein tyrosine phosphatase for cell adhesion and its mutations in gastrointestinal cancers.

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Since the level of tyrosine phosphorylation is determined by the balance between the actions of both protein tyrosine kinases and protein tyrosine phosphatases (PTPases), not only the unregulated activation of PTKs but also the inactivation of PTPases may be involved in the malignant transformation of gastrointestinal cells. PTPH1 is a human non-transmembrane-type PTPase that has recently been molecularly cloned. This enzyme contains an Ezrin-like structure and a PDZ domain in its N-terminal region. Since Ezrin-like structures are suggested to be involved in cell adhesion, PTPH1 may locate at the cell adhesion sites and regulate cell adhesion through the control of tyrosine phosphorylation of proteins at cell adhesion sites. In this study, we investigated the physiological roles of PTPH1 and clinical applications of PTPH1. (1) PTPH1 located at cell adhesion sites. (2) Transfection of PTPH1 mutants into cultured cells did not show any changes in terms of cell adhesion. We will further examine the effect of microinjection of antibody to PTPH1 into cultured cells. (3) With the use of RT-P CR, we have examined the mutations of PTPH1 gene in various gastrointestinal cancers. We have found several mutations in PTPH1 gene in gastrointestinal cancer sample. We will further investigate whether the mutations found in gastrointestinal cancers results in oncogenesis of these cancers. In addition, we will try to identify the proteins bound to the Ezrin domain or the PDZ domain of PTPH1 by the yeast two-hybrid system.