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Etk, also named Bmx, is a member of the Tec tyrosine kinase family, which is characterized by a multimodular structure including a pleckstrin homology (PH) domain, an SH3 domain, an SH2 domain, and a catalytic domain. The signaling mechanisms regulating Etk kinase activity remain largely unknown. To identify factor(s) regulating Etk activity, we used the PH domain and a linker region of Etk as a bait for a yeast two-hybrid screen. Three independent clones encoding protein-tyrosine phosphatase D1 (PTPD1) fragments were isolated. The binding of PTPD1 to Etk is specific since PTPD1 cannot associate with either the Akt PH domain or lamin. In vitro and in vivo binding studies demonstrated that PTPD1 can interact with Etk and that residues 726-848 of PTPD1 are essential for this interaction. Deletion analysis of Etk indicated that the PH domain is essential for PTPD1 interaction. Furthermore, the Etk-PTPD1 interaction stimulated the kinase activity of Etk, resulting in an increased phosphotyrosine content in both factors. The Etk-PTPD1 interaction also increased Stat3 activation. The effect of PTPD1 on Etk activation is specific since PTPD1 cannot potentiate Jak2 activity upon Stat3 activation. In addition, Tec (but not Btk) kinase can also be activated by PTPD1. Taken together, these findings indicate that PTPD1 can selectively associate with and stimulate Tec family kinases and modulate Stat3 activation.

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This study presents the distribution of Cu, Zn, Pb, Cd, Hg and As in various marine organisms collected along the western coast of Taiwan from 1991 to 1998, and also evaluates the time variation of Cu in oysters before (1980-85) and after (1986-98) the "green oyster" incident. The results show that relatively high geometric mean (GM) concentrations of Cu, Zn, Pb, Cd, As and Hg were generally found in Crassostrea gigas (Cu=229 microg/g, Zn=783 microg/g), Gomphina aeguialtera (Pb=30.3 microg/g), Tegillarca granosa (Cd=2.85 microg/g), Thais clavigera (As=96.9 microg/g) and Parapenaeopsis cornuta (Hg=1.35 microg/g), respectively. Especially, maximum Cu and Zn concentrations (GM=229 and 783 microg/g, respectively) in oysters (C. gigas) from different culture areas were much higher than those of the other organisms by about 1.13-458 and 2.40-63.7 times, respectively. Similarly, rock-shells (Thais clavigera) had a high capacity for accumulating Cu (GM=202 microg/g) and Zn (GM=326 microg/g) under the same physico-chemical conditions. The highest GM Cu and Zn concentrations of 1108 (range from 113 to 2806) and 1567 (range from 303 to 3593) microg/g were obtained in oysters from the Hsiangshan coastal area, one of the most important oyster culture areas in Taiwan. However, the highest GM Cd and As concentrations of 6.82 and 19.3 microg/g were found in oysters from the Machu Islands. Mean Cu concentrations in the oysters from the Erhjin Chi estuary declined from 2194+/-212 microg/g in 1986-90 to 545 microg/g (GM) in 1991-96. In the Hsiganshan area, GM Cu concentrations of 909 microg/g (1991-96) and 1351 microg/g (1997-98) in oysters were significantly higher than those of 201 microg/g (1980-85) and 682 microg/g (1986-90). The gradually increasing levels of Cu and Zn in the oysters from the Hsiangshan area have been observed year by year.

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The purpose of this paper is to describe the impact of metal pollution on the main seafood and assess the potential health risk from consuming the contaminated seafood in Taiwan. The results of geometric mean (GM) metal concentrations in various seafood showed that the copper, zinc, and arsenic concentrations in oysters were significantly (p < 0.001) higher than those in the other seafood by about 1,057, 74.3, and 56.2 times, respectively. The green color found in the oysters was due to high GM copper and zinc concentrations of 909 (ranging from 113-2,805) and 1,293 (ranging from 303-3,593) microg/g dry wt, respectively. In addition, using a maximum consumption rate of 139 g/day of oysters for individuals, calculations yield target hazard quotients (daily intake/reference dose) of below 1 for cadmium and mercury and high values of 1.61, 9. 33, and 1.77 for inorganic arsenic, copper, and zinc in adults, respectively. The various lifetime cancer risks for inorganic arsenic (maximum exposed individuals risk ranging from 9.93 x 10(-6) to 3.11 x 10(-4)) might be caused by consuming different seafood in Taiwan. The highest risk estimate for inorganic arsenic was 5.10 x 10(-4) for consumption of oysters by Machu Islands residents. The long-term exposure of metals through consumption of oysters, especially for some high-risk groups, could be dangerous. Taking inorganic arsenic for example, a 10(-6) upper limit on lifetime risk as the health protection standard would require maximum oyster residue levels of approximately 0.0076-0.056 microg/g wet wt, for consumption rates of 139-18.6 g/d. In the light of known risks to public health, the government should issue an immediate warning to the public to refrain from eating all seafood harvested from the Taiwan coastal areas, especially the Hsiangshan area and the Machu Islands.

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