Focal Adhesion Kinase Regulates Critical Functions in Hematopoiesis

• Published in: Blood 2007-11, Vol.110 (11), p.1407-1407
• Main Authors: Vemula, Sasidhar, Abratigue, Benjamin P., Gandra, Premchand, O'Malley, John T., Ahyi, Ayek-Nati N., Stritesky, Gretta, Yeh, Norman, Kaplan, Mark, Beggs, Hillary, Kapur, Reuben
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V110.11.1407.1407

Focal adhesion kinase (FAK) initially identified as a unique cytoplasmic tyrosine kinase involved in focal adhesions, has been studied extensively in fibroblasts. In these cells, FAK has been shown to play an essential role in bridging signals between integrin and growth factor receptors such as the PDGF and the EGF receptor. In fibroblasts, FAK localizes to regions of the cell that attach to the extracellular matrix and coordinates signals from integrins, cytokines, growth factor receptors, and oncogenes. In some tumors, FAK is over-expressed or constitutively activated, which correlates with increased motility, invasiveness, and proliferation. More recently, expression of FAK in acute myeloid leukemia was associated with enhanced blast migration, increased cellularity, and poor prognosis. However, virtually nothing is known about FAKs role in normal hematopoiesis. FAK is expressed in blood cells, including in bone marrow derived KIT+, Gr-1+, Mac-1+, CD4+, CD8+ and B220+ cells. To determine how loss of FAK affects hematopoiesis, we have generated a mouse model with hematopoietic restricted deletion of FAK. We deleted FAK in bone marrow cells by crossing the FAK-flox mice to Mx.Cre+ expressing mice and by treating Mx.cre+FAK+/+ and Mx.cre+FAKflox/flox mice with poly (I)-poly(C) and then analyzing mice 1 month after the last injection. After one month of poly(I)-poly(C) induction, the progeny failed to express detectable levels of FAK in bone marrow, spleen as well as in bone marrow derived macrophages as determined by PCR and western blotting. Evaluation of peripheral blood counts in control and FAK deleted mice revealed modest but significant differences in different lineages (WBC k/μl: FAK; 14 vs. FAK−/−; 10.3, n=7, *p