Phase separation ability and phosphatase activity of the SHP1-R360E mutant

Qichen Zhang; Wenna Kong; Tianxin Zhu; Guangya Zhu; Jidong Zhu; Xiangyu Kong; Yiqi Du

doi:10.1016/j.bbrc.2022.02.070

Phase separation ability and phosphatase activity of the SHP1-R360E mutant

Biochem Biophys Res Commun. 2022 Apr 16:600:150-155. doi: 10.1016/j.bbrc.2022.02.070. Epub 2022 Feb 22.

Authors

Qichen Zhang¹, Wenna Kong², Tianxin Zhu², Guangya Zhu³, Jidong Zhu⁴, Xiangyu Kong⁵, Yiqi Du⁶

Affiliations

¹ Department of Gastroenterology, Changhai Hospital, Naval Medical University, Shanghai, 200433, China.
² Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, 201203, China; University of the Chinese Academy of Sciences, Beijing 100049, China.
³ Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, 201203, China.
⁴ Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, 201203, China; Etern Biopharma Co. Ltd., Shanghai, 201203, China. Electronic address: zhujd@sioc.ac.cn.
⁵ Department of Gastroenterology, Changhai Hospital, Naval Medical University, Shanghai, 200433, China. Electronic address: xiangyukong185@hotmail.com.
⁶ Department of Gastroenterology, Changhai Hospital, Naval Medical University, Shanghai, 200433, China. Electronic address: duyiqi006@126.com.

PMID: 35219918
DOI: 10.1016/j.bbrc.2022.02.070

Abstract

SHP1 is a non-receptor protein tyrosine phosphatase that is widely expressed in hematopoietic cells such as white blood cells, neutrophils, and immune cells. SHP1 can regulate the occurrence and differentiation of immune cells and plays an important role as a tumor suppressor. Previous studies have suggested that SHP2, the homologous protein of phosphatase SHP1, can undergo liquid-liquid phase separation (LLPS). Therefore, in this study, we investigated if SHP1 is also capable of LLPS. To the best of our knowledge, our study is the first to reveal that SHP1 has the ability to undergo LLPS. In addition, we identified an important residue, SHP1-R360E, that can completely inhibit the LLPS ability of SHP1, but this mutation has no remarkable effect on SHP1's enzymatic activity. This allows us to explore the phosphatase activity and phase separation ability of SHP1 separately, providing a basis for future exploration of the phase separation mechanism of phosphatases.

Keywords: Liquid-liquid phase separation; Mutant; Phosphatase; SHP1.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Differentiation
Protein Tyrosine Phosphatase, Non-Receptor Type 11* / genetics
Protein Tyrosine Phosphatase, Non-Receptor Type 11* / metabolism
Protein Tyrosine Phosphatase, Non-Receptor Type 6 / genetics
Protein Tyrosine Phosphatase, Non-Receptor Type 6 / metabolism

Substances

Protein Tyrosine Phosphatase, Non-Receptor Type 11
Protein Tyrosine Phosphatase, Non-Receptor Type 6