Receptor-type protein tyrosine phosphatase α (RPTPα) is an important positive regulator of SRC kinase activation and a known promoter of cancer growth, fibrosis, and arthritis. The domain structure of RPTPs comprises an extracellular region, a transmembrane helix, and two tandem intracellular catalytic domains referred to as D1 and D2. The D2 domain of RPTPs is believed to mostly play a regulatory function; however, no regulatory model has been established for RPTPα-D2 or other RPTP-D2 domains. Here, we solved the 1.8 Å resolution crystal structure of the cytoplasmic region of RPTPα, encompassing D1 and D2, trapped in a conformation that revealed a possible mechanism through which D2 can allosterically inhibit D1 activity. Using a D2-truncation RPTPα variant and mutational analysis of the D1/D2 interfaces, we show that D2 inhibits RPTPα phosphatase activity and identified a 405PFTP408 motif in D1 that mediates the inhibitory effect of D2. Expression of the gain-of-function F406A/T407A RPTPα variant in HEK293T cells enhanced SRC activation, supporting the relevance of our proposed D2-mediated regulation mechanism in cell signaling. There is emerging interest in the development of allosteric inhibitors of RPTPs but a scarcity of validated allosteric sites for RPTPs. The results of our study not only shed light on the regulatory role of RPTP-D2 domains, but also provide a potentially useful tool for the discovery of chemical probes targeting RPTPα and other RPTPs.
With strong national advocacy and policy guidance, the coordination of economy and environment has become an issue that cannot be ignored nowadays. Proper understanding and handling of the relationship between economic development and environmental protection is conducive to promoting the high-quality development of China's economy and helping enterprises to take environmental benefits into account while pursuing economic benefits. In this context, based on multiple theoretical and empirical studies, this paper selects all A-share listed companies from 2011-2020 as the research object, constructs a multiple regression model with fixed industry and year, and innovatively explores the impact of corporate environmental performance on trait risk and its mechanism of action. The study shows that corporate environmental performance significantly reduces idiosyncratic risk, while corporate information quality mediates the relationship between the two, and media pressure positively moderates the relationship between corporate environmental performance and information disclosure quality. In addition, this paper also replaces the original explanatory variables with Chinese three-factor model regression residuals to estimate corporate idiosyncratic risk, and expands the explanatory variables to ESG to conduct robustness tests on all research hypotheses, which promotes the development of the investigation of the mechanism of ESG's influence on idiosyncratic risk. Based on the results of the above analysis, this paper is able to provide impetus for the improvement of the intrinsic environmental performance of companies and the external environmental concern coverage of media reports, and make marginal contributions to the promotion of high-quality economic development.
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