Engagement of PSGL-1 upregulates CSF-1 transcription via a mechanism that may involve Syk.
PSGL-1, the optimal selectin ligand demonstrated by in vivo studies to date, is an essential adhesive molecule mediating the rolling of leukocytes on the endothelial cells and the recruitment of leukocytes to the inflamed tissue. Recent studies demonstrated, in addition to its direct role in capture of leukocytes from the bloodstream, PSGL-1 also functions as a signal-transducing receptor and initiates a series of intracellular signal events during the activation of leukocytes. Our present work showed antibody engagement of PSGL-1 upregulated the transcriptional activity of CSF-1 promotor and increased the endogenous expression of CSF-1 mRNA in Jurkat cell. Overexpression of wild-typed non-receptor tyrosine kinase Syk, but not kinase dead mutant of Syk, promoted the upregulation of the transcriptional activity of CSF-1 promoter caused by antibody engagement of PSGL-1. Additionally, special inhibitor of Syk Piceatannol suppressed the increase of CSF-1 mRNA caused by the engagement of PSGL-1. The results suggest that signal transducted by PSGL-1 upregulate the transcriptional activity of CSF-1, and non-receptor tyrosine kinase Syk participates in this pathway.
Ba
Xue-Qing
XQ
Institute of Genetics and Cytology, Northeast Normal University, Changchun 130024, China.
Chen
Cui-Xia
CX
Xu
Ting
T
Cui
Ling-Ling
LL
Gao
Yan-Guang
YG
Zeng
Xian-Lu
XL
D004792:Enzyme Precursors / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D019169:Jurkat Cells; D016173:Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011505:Protein-Tyrosine Kinases / Q000276:immunology / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology*; D000072377:Syk Kinase; D014158:Transcription, Genetic; D015854:Up-Regulation
D004792:Enzyme Precursors; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; C084882:P-selectin ligand protein; D012333:RNA, Messenger; D016173:Macrophage Colony-Stimulating Factor; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase