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Janus kinase 2 is involved in stromal cell–derived factor-1α–induced tyrosine phosphorylation of focal adhesion proteins and migration of hematopoietic progenitor cells
Abstract
Stromal cell–derived factor-1 (SDF-1), the ligand for the CXCR4 receptor, is a highly efficacious chemoattractant for CD34+hematopoietic progenitor cells. However, the SDF-1/CXCR4 signaling pathways that regulate hematopoiesis are still not well defined. This study reports that SDF-1α can stimulate the tyrosine phosphorylation of Janus kinase 2 (JAK2) and other members of the JAK/signal transduction and activation of transcription (STAT) family, including JAK1, tyrosine kinase 2, STAT2, and STAT4 in the human progenitor cell line, CTS. SDF-1α stimulation of these cells also enhanced the association of JAK2 with phosphatidylinositol 3 (PI3)-kinase. This enhanced association was abolished by pretreatment of cells with AG490, a specific JAK2 inhibitor. Furthermore, pretreatment of CTS cells with AG490 significantly inhibited SDF-1α–induced PI3-kinase activity, and inhibition of JAK2 with AG490 ablated the SDF-1α–induced tyrosine phosphorylation of multiple focal adhesion proteins (including focal adhesion kinase, related adhesion focal tyrosine kinase, paxillin, CrkII, CrkL, and p130Cas). Chemotaxis assays showed that inhibition of JAK2 diminished SDF-1α–induced migration in both CTS cells and CD34+ human bone marrow progenitor cells. Hence, these results suggest that JAK2 is required for CXCR4 receptor-mediated signaling that regulates cytoskeletal proteins and cell migration through PI3-kinase pathways in hematopoietic progenitor cells.
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Citations
Cited by
CXCL12 (SDF-1)/CXCR4 Pathway in Cancer
Teicher, B. A., & Fricker, S. P. (2010) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-09-2329 · Cited by 1,449
Kucia, M., Reca, R., Miekus, K., Wanzeck, J., Wojakowski, W., Janowska‐Wieczorek, A., Ratajczak, J., & Ratajczak, M. Z. (2005) · STEM CELLS · doi:10.1634/stemcells.2004-0342 · Cited by 759
CXCR4–SDF-1 Signalling, Locomotion, Chemotaxis and Adhesion
Kucia, M., Jankowski, K., Reca, R., Wysoczynski, M., Bandura, L., Allendorf, D. J., Zhang, J., Ratajczak, J., & Ratajczak, M. Z. (2004) · Journal of Molecular Histology · doi:10.1023/b:hijo.0000032355.66152.b8 · Cited by 698
Tang, Y. L., Zhu, W., Cheng, M., Chen, L., Zhang, J., Sun, T., Kishore, R., Phillips, M. I., Losordo, D. W., & Qin, G. (2009) · Circulation Research · doi:10.1161/circresaha.109.197723 · Cited by 363
de Gorter, D. J. J., Beuling, E. A., Kersseboom, R., Middendorp, S., van Gils, J. M., Hendriks, R. W., Pals, S. T., & Spaargaren, M. (2007) · Immunity · doi:10.1016/j.immuni.2006.11.012 · Cited by 285
Metadata
- Authors
- Zhang, X.-F., Wang, J.-F., Matczak, E., Proper, J., & Groopman, J. E.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2001-06-01
- Volume
- 97
- Issue
- 11
- Pages
- 3342-3348
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2004289105
- Cited by
- 173
- References
- 0
- FWCI
- 5.70
- Type
- journal article
- Language
- en
- Open access
- closed
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- Zhang, X.-F., Wang, J.-F., Matczak, E., Proper, J., & Groopman, J. E. (2001). Janus kinase 2 is involved in stromal cell–derived factor-1α–induced tyrosine phosphorylation of focal adhesion proteins and migration of hematopoietic progenitor cells. Blood. https://doi.org/10.1182/blood.v97.11.3342
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