|
|
Blood, 1 June 2006, Vol. 107, No. 11, pp. 4234-4239.
Prepublished online as a Blood First Edition Paper on February 7, 2006; DOI 10.1182/blood-2005-08-3343.
 Previous Article | Next Article 
Submitted August 18, 2005
Accepted January 25, 2006
Integrin inhibition through Lyn-dependent crosstalk from CXCR4 chemokine receptor in normal human CD34+ marrow cells
Yuji Nakata, Brian Tomkowicz, Alan M Gewirtz, and Andrzej Ptasznik*
Division of Hematology & Oncology, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
* Corresponding author; email: andrzejp{at}mail.med.upenn.edu.
We studied the effects of Lyn ablation on CXCR4 receptor-mediated migration and adhesion of hematopoietic precursors. Down-regulation of Lyn expression with siRNA greatly reduced CXCR4-dependent hematopoietic cell movement, and increased cell adherence to stroma. This increase was associated with the up-regulated expression of activation-dependent epitopes of the  2 integrin LFA-1 and was prevented by antibodies that selectively block cell adhesion mediated by ICAM-1. Attachment to surfaces coated with ICAM-1 was also enhanced in Lyn-depleted hematopoietic cells, as compared to Lyn-expressing cells. Functional rescue experiments with Lyn siRNA targeting the 3'UTR indicated that the observed effects can be attributed directly to specific inhibition of Lyn. Our results show that in chemokine-stimulated hematopoietic cells Lyn kinase is a positive regulator of cell movement while negatively regulating adhesion to stromal cells by inhibiting the ICAM-1-binding activity of 2 integrins. These results provide a molecular mechanism for crosstalk between the chemokine receptor CXCR4 and 2 integrins. This crosstalk may allow chemokine receptors to modulate the arrest of rolling hematopoietic precursors on the surface of bone marrow stromal cells.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
R. Cheung, M. Malik, V. Ravyn, B. Tomkowicz, A. Ptasznik, and R. G. Collman
An arrestin-dependent multi-kinase signaling complex mediates MIP-1{beta}/CCL4 signaling and chemotaxis of primary human macrophages
J. Leukoc. Biol.,
October 1, 2009;
86(4):
833 - 845.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Malik, Y.-Y. Chen, M. F. Kienzle, B. E. Tomkowicz, R. G. Collman, and A. Ptasznik
Monocyte Migration and LFA-1-Mediated Attachment to Brain Microvascular Endothelia Is Regulated by SDF-1{alpha} through Lyn Kinase
J. Immunol.,
October 1, 2008;
181(7):
4632 - 4637.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Guan, Z. Zhou, G. E. Gallick, S.-F. Jia, J. Morales, A. K. Sood, S. J. Corey, and E. S. Kleinerman
Targeting Lyn inhibits tumor growth and metastasis in Ewing's sarcoma
Mol. Cancer Ther.,
July 1, 2008;
7(7):
1807 - 1816.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y.-Y. Chen, M. Malik, B. E. Tomkowicz, R. G. Collman, and A. Ptasznik
BCR-ABL1 alters SDF-1{alpha}-mediated adhesive responses through the {beta}2 integrin LFA-1 in leukemia cells
Blood,
May 15, 2008;
111(10):
5182 - 5186.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Forde, B. J. Tye, S. E. Newey, M. Roubelakis, J. Smythe, C. P. McGuckin, R. Pettengell, and S. M. Watt
Endolyn (CD164) modulates the CXCL12-mediated migration of umbilical cord blood CD133+ cells
Blood,
March 1, 2007;
109(5):
1825 - 1833.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
