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RANTES (CCL5) induces a CCR5-dependent accelerated shedding of syndecan-1 (CD138) and syndecan-4 from HeLa cells and forms complexes with the shed ectodomains of these proteoglycans as well as with those of CD44
- Source :
- Glycobiology. 15:119-130
- Publication Year :
- 2004
- Publisher :
- Oxford University Press (OUP), 2004.
-
Abstract
- We recently demonstrated that RANTES forms complexes with CCR5, syndecan-1 (SD-1), SD-4, and CD44 expressed by human primary macrophages and that SD-1 and SD-4 but neither CD44 nor SD-2 coimmunoprecipitate with CCR5. Here we show that RANTES directly binds in a glycosaminoglycan-dependent manner to SD-1, SD-4, and CD44. Moreover, RANTES accelerates the shedding of SD-1 and SD-4 ectodomains from HeLa cells expressing CCR5 and, by contrast, has no effect on the constitutive shedding of CD44 from these cells. These accelerated sheddings are prevented by the MEK1/2 inhibitor, U0126, and by the protein kinase C inhibitor bisindolylmaleimide I. This indicates that both MAP kinase--and protein kinase C-dependent signaling pathways are involved in these RANTES-induced accelerated sheddings. RANTES also induces a decreased expression of SD-1 and SD-4 by HeLa cells expressing CCR5 and on the contrary an increased expression of CD44 by these cells. By contrast, RANTES neither accelerates the shedding of SD-1 and SD-4 ectodomains from HeLa cells lacking CCR5, nor changes the SD-1-, SD-4-, and CD44-plasma membrane expressions of these cells. CCR5 is therefore involved in the RANTES-induced accelerated shedding of SD-1 and SD-4 ectodomains. Nevertheless, the fact that RANTES stimulates in Hela cells (expressing or lacking CCR5) the mRNA synthesis of SD-1 and SD-4 indicates that the molecular events that follow the synthesis of these proteoglycans differ, according to the presence or not of CCR5. Finally, RANTES forms GAG-dependent complexes with the shed ectodomains of SD-1 and SD-4 as well as with those of CD44. The role of these events in the pathophysiology of RANTES deserves further study.
- Subjects :
- Syndecans
Receptors, CCR5
MAP Kinase Signaling System
Gene Expression
Transfection
Biochemistry
Syndecan 1
HeLa
Humans
Receptor
Protein kinase A
Chemokine CCL5
Protein kinase C
Membrane Glycoproteins
biology
CD44
biology.organism_classification
Molecular biology
Protein Structure, Tertiary
Hyaluronan Receptors
biology.protein
Proteoglycans
Syndecan-4
Syndecan-1
Signal transduction
HeLa Cells
Protein Binding
Subjects
Details
- ISSN :
- 14602423
- Volume :
- 15
- Database :
- OpenAIRE
- Journal :
- Glycobiology
- Accession number :
- edsair.doi.dedup.....f3ca0eafb451934e8b302270c444fe98