1. Academic Validation
  2. PC3-secreted microprotein is a novel chemoattractant protein and functions as a high-affinity ligand for CC chemokine receptor 2

PC3-secreted microprotein is a novel chemoattractant protein and functions as a high-affinity ligand for CC chemokine receptor 2

  • J Immunol. 2014 Feb 15;192(4):1878-86. doi: 10.4049/jimmunol.1300758.
Xiaolei Pei 1 Qianying Sun Yan Zhang Pingzhang Wang Xinjian Peng Changyuan Guo Enquan Xu Yi Zheng Xiaoning Mo Jing Ma Dixin Chen Yang Zhang Yingmei Zhang Quansheng Song Shuai Guo Taiping Shi Zhixin Zhang Dalong Ma Ying Wang
Affiliations

Affiliation

  • 1 Department of Immunology, School of Basic Medical Sciences, and Key Laboratory of Medical Immunology of Ministry of Health, Peking University Health Science Center, Beijing 100191, China;
Abstract

PC3-secreted microprotein (PSMP) or microseminoprotein is a newly discovered secreted protein whose function is currently unknown. In this study, PSMP was found to possess chemotactic ability toward monocytes and lymphocytes, and its functional receptor was identified as CCR2B. PSMP was identified as a chemoattractant protein from a PBMC chemoattractant platform screen that we established. The mature secreted PSMP was able to chemoattract human peripheral blood monocytes, PBLs, and CCR2B-expressing THP-1 cells, but not peripheral blood neutrophils, even though it does not contain the classical structure of chemokines. CCR2B was identified as one receptor for PSMP-mediated chemotaxis by screening HEK293 cells that transiently expressed classical chemokine receptors; results obtained from the chemotaxis, calcium flux, receptor internalization, and radioligand-binding assays all confirmed this finding. To further identify the major function of PSMP, we analyzed its expression profile in tissues. PSMP is highly expressed in benign prostatic hyperplasia and in some prostate cancers, and can also be detected in breast tumor tissue. In response to PSMP stimulation, phosphorylated ERK levels downstream of CCR2B signaling were upregulated in the PC3 cell line. Taken together, our data collectively suggest that PSMP is a chemoattractant protein acting as a novel CCR2 ligand that may influence inflammation and Cancer development.

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