PC3-secreted microprotein is a novel chemoattractant protein and functions as a high-affinity ligand for CC chemokine receptor 2.
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.
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;
Xiaolei
X
Pei
Qianying
Q
Sun
Yan
Y
Zhang
Pingzhang
P
Wang
Xinjian
X
Peng
Changyuan
C
Guo
Enquan
E
Xu
Yi
Y
Zheng
Xiaoning
X
Mo
Jing
J
Ma
Dixin
D
Chen
Yang
Y
Zhang
Yingmei
Y
Zhang
Quansheng
Q
Song
Shuai
S
Guo
Taiping
T
Shi
Zhixin
Z
Zhang
Dalong
D
Ma
Ying
Y
Wang
D001943:Breast Neoplasms / Q000378:metabolism; D002460:Cell Line; D002630:Chemotactic Factors / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D057809:HEK293 Cells; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D008024:Ligands; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D009000:Monocytes / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism*; D009504:Neutrophils / Q000378:metabolism; D010766:Phosphorylation; D011470:Prostatic Hyperplasia / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism; D011485:Protein Binding; D054390:Receptors, CCR2 / Q000378:metabolism*
D002630:Chemotactic Factors; D048049:Extracellular Signal-Regulated MAP Kinases; D008024:Ligands; D009363:Neoplasm Proteins; D054390:Receptors, CCR2; C519082:MSMP protein, human