Dampened ERK signaling in hematopoietic progenitor cells in rheumatoid arthritis
Copyright © 2012 Elsevier Inc. All rights reserved.
| Veröffentlicht in: | Clinical immunology (Orlando, Fla.). - 1999. - 143(2012), 1 vom: 30. Apr., Seite 73-82 |
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| 1. Verfasser: | |
| Weitere Verfasser: | , , , |
| Format: | Online-Aufsatz |
| Sprache: | English |
| Veröffentlicht: |
2012
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| Zugriff auf das übergeordnete Werk: | Clinical immunology (Orlando, Fla.) |
| Schlagworte: | Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Antigens, CD34 Cyclins Cytokines Hematopoietic Cell Growth Factors Interleukin-3 Receptor alpha Subunit Interleukin-6 Receptor alpha Subunit Proto-Oncogene Proteins c-myc mehr... |
| Zusammenfassung: | Copyright © 2012 Elsevier Inc. All rights reserved. In rheumatoid arthritis (RA), hematopoietic progenitor cells (HPC) have age-inappropriate telomeric shortening suggesting premature senescence and possible restriction of proliferative capacity. In response to hematopoietic growth factors RA-derived CD34(+) HPC expanded significantly less than age-matched controls. Cell surface receptors for stem cell factor (SCF), Flt 3-Ligand, IL-3 and IL-6 were intact in RA HPC but the cells had lower transcript levels of cell cycle genes, compatible with insufficient signal strength in the ERK pathway. Cytokine-induced phosphorylation of ERK1/2 was diminished in RA HPC whereas phosphorylated STAT3 and STAT5 molecules accumulated to a similar extent as in controls. Confocal microscopy demonstrated that the membrane-proximal colocalization of K-Ras and B-Raf was less efficient in RA-derived CD34(+) cells. Thus, hyporesponsiveness of RA HPC to growth factors results from dampening of the ERK signaling pathways; with a defect localized in the very early steps of the ERK signaling cascade |
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| Beschreibung: | Date Completed 11.05.2012 Date Revised 29.05.2025 published: Print-Electronic Citation Status MEDLINE |
| ISSN: | 1521-7035 |
| DOI: | 10.1016/j.clim.2012.01.007 |