NDLI: Essential role for focal adhesion kinase in regulating stress hematopoiesis

Content Provider	PubMed Central
Author	Vemula, Sasidhar Ramdas, Baskar Hanneman, Philip Martin, Joseph Beggs, Hilary E. Kapur, Reuben
Abstract	Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that has been extensively studied in fibroblasts; however its function in hematopoiesis remains an enigma. FAK is thought to be expressed in myeloid and erythroid progenitors, and its expression is enhanced in response to cytokines such as granu-locyte macrophage colony-stimulating factor. Furthermore, bone marrow cells cultured in granulocyte macrophage colony-stimulating factor show active migration and chemoattractant-induced polarization, which correlates with FAK induction. While loss of FAK in mice results in embryonic lethality, we have deleted FAK in the adult bone marrow. We show an essential role for FAK in regulating hemolytic, myelotoxic, as well as acute inflammatory stress responses in vivo. In vitro, loss of FAK in erythroid and myeloid progenitor's results in impaired cytokine induced growth and survival, as well as defects in the activation and expression of antiapoptotic proteins caspase 3 and Bcl-xL. Additionally, reduced migration and adhesion of myeloid cells on extracellular matrix proteins, as well as impaired activation of Rac GTPase is also observed in the absence of FAK. Our studies reveal an essential role for FAK in integrating growth/survival and adhesion based functions in myeloid and erythroid cells predominantly under conditions of stress.
Related Links	http://dx.doi.org/10.1182/blood-2010-01-262790
Ending Page	4115
Page Count	13
Starting Page	4103
File Format	PDF
ISSN	00064971
e-ISSN	15280020
Journal	Blood
Issue Number	20
Volume Number	116
Language	English
Publisher	American Society of Hematology
Publisher Date	2010-11-18
Access Restriction	Open
Rights Holder	American Society of Hematology
Subject Keyword	Immunology Cell Biology Biochemistry Hematology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cell Biology Hematology Biochemistry Immunology

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