Focal adhesion kinase is required for CXCL12-induced chemotactic and pro-adhesive responses in hematopoietic precursor cells

A. M. Glodek, Y. Le, Derek M Dykxhoorn, S. Y. Park, G. Mostoslavsky, R. Mulligan, J. Lieberman, H. E. Beggs, M. Honczarenko, L. E. Silberstein

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Hematopoietic stem/progenitor cells (HSC/P) reside in the bone marrow in distinct anatomic locations (niches) to receive growth, survival and differentiation signals. HSC/P localization and migration between niches depend on cell/cell and cell/matrix interactions, which result from the cooperation of cytokines, chemokines and adhesion molecules. The CXCL12-CXCR4 pathway, in particular, is essential for myelopoiesis and B lymphopoiesis but the molecular mechanisms of CXCL12 action remain unclear. We previously noted a strong correlation between prolonged CXCL12-mediated focal adhesion kinase (FAK) phosphorylation and sustained pro-adhesive responses in progenitor B cells, but not in mature B cells. Although FAK has been well studied in adherent fibroblasts, its function in hematopoietic cells is not defined. We used two independent approaches to reduce FAK expression in (human and mouse) progenitor cells. RNA interference (RNAi)-mediated FAK silencing abolished CXCL12-induced responses in human pro-B leukemia, REH cells. FAK-deficient REH cells also demonstrated reduced CXCL12-induced activation of the GTPase Rap1, suggesting the importance of FAK in CXCL12-mediated integrin activation. Moreover, in FAKflox/flox hematopoietic precursor cells, Cre-mediated FAK deletion resulted in impaired CXCL12-induced chemotaxis. These studies suggest that FAK may function as a key intermediary in signaling pathways controlling hematopoietic cell lodgment and lineage development.

Original languageEnglish
Pages (from-to)1723-1732
Number of pages10
JournalLeukemia
Volume21
Issue number8
DOIs
StatePublished - Aug 1 2007
Externally publishedYes

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Focal Adhesion Protein-Tyrosine Kinases
Adhesives
Hematopoietic Stem Cells
Lymphopoiesis
Myelopoiesis
B-Cell Leukemia
B-Lymphoid Precursor Cells
GTP Phosphohydrolases
Cell Lineage
Chemotaxis
RNA Interference
Chemokines
Integrins
Cell Communication
B-Lymphocytes
Stem Cells
Fibroblasts
Bone Marrow
Phosphorylation
Cytokines

ASJC Scopus subject areas

  • Hematology
  • Cancer Research

Cite this

Focal adhesion kinase is required for CXCL12-induced chemotactic and pro-adhesive responses in hematopoietic precursor cells. / Glodek, A. M.; Le, Y.; Dykxhoorn, Derek M; Park, S. Y.; Mostoslavsky, G.; Mulligan, R.; Lieberman, J.; Beggs, H. E.; Honczarenko, M.; Silberstein, L. E.

In: Leukemia, Vol. 21, No. 8, 01.08.2007, p. 1723-1732.

Research output: Contribution to journalArticle

Glodek, AM, Le, Y, Dykxhoorn, DM, Park, SY, Mostoslavsky, G, Mulligan, R, Lieberman, J, Beggs, HE, Honczarenko, M & Silberstein, LE 2007, 'Focal adhesion kinase is required for CXCL12-induced chemotactic and pro-adhesive responses in hematopoietic precursor cells', Leukemia, vol. 21, no. 8, pp. 1723-1732. https://doi.org/10.1038/sj.leu.2404769
Glodek, A. M. ; Le, Y. ; Dykxhoorn, Derek M ; Park, S. Y. ; Mostoslavsky, G. ; Mulligan, R. ; Lieberman, J. ; Beggs, H. E. ; Honczarenko, M. ; Silberstein, L. E. / Focal adhesion kinase is required for CXCL12-induced chemotactic and pro-adhesive responses in hematopoietic precursor cells. In: Leukemia. 2007 ; Vol. 21, No. 8. pp. 1723-1732.
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