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(5) atrophy of muscles in hands and feet

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On the other hand, EGFR signaling is negatively regulated by protein tyrosine phosphatase 1B (PTP1B), which catalyzes tyrosine dephosphorylation of activated EGFR, and the inhibition of PTP1B has been reported to evoke a ligand-independent activation of EGFR.Citation 44,45 ) Recent findings also indicate that PTP1B activity is modulated by post-translational modification, such as oxidation and alkylation of an extremely reactive cysteine residue at the catalytic center.Citation 46 ) On the basis of these facts, we have elucidated that PQQ inhibits PTP1B through the oxidation of catalytic cysteinyl thiol by H 2 O 2 produced during its redox cycling, thereby inducing the ligand-independent activation of EGFR (Fig