Regulation of Lymphoid Tyrosine Phosphatase Activity: Inhibition of the Catalytic Domain by the Proximal Interdomain

详细信息    查看全文

• 作者：Yingge Liu ; Stephanie M. Stanford ; Sonali P. Jog ; Edoardo Fiorillo ; Valeria Orr ; Lucio Comai ; Nunzio Bottini
• 刊名：Biochemistry
• 出版年：2009
• 出版时间：August 11, 2009
• 年：2009
• 卷：48
• 期：31
• 页码：7525-7532
• 全文大小：955K
• 年卷期：v.48,no.31(August 11, 2009)
• ISSN：1520-4995

文摘

The lymphoid tyrosine phosphatase LYP, encoded by the PTPN22 gene, recently emerged as a major player and candidate drug target for human autoimmunity. The enzyme includes a classical N-terminal protein tyrosine phosphatase catalytic domain and a C-terminal PEST-enriched domain, separated by an 300-amino acid interdomain. Little is known about the regulation of LYP. Herein, by analysis of serial truncation mutants of LYP, we show that the phosphatase activity is strongly inhibited by protein regions C-terminal to the catalytic domain. We mapped the minimal inhibitory region to the proximal portion of the interdomain. We show that the activity of LYP is inhibited by an intramolecular mechanism, whereby the proximal portion of the interdomain directly interacts with the catalytic domain and reduces its activity.