Nuclear import of N-terminal FAK by activation of the FcepsilonRI receptor in RBL-2H3 cells.
As FAK integrates membrane receptor signalling, yet is also found in the nucleus, we investigated whether nuclear FAK is regulated by membrane receptor activation. Activation of the mast cell FcepsilonRI receptor leads to the release and synthesis of inflammatory mediators as well as increased proliferation and survival. Using RBL-2H3 basophilic leukaemia cells, FAK and the FcepsilonRI receptor were co-localised following cross-linking of IgE with antigen. This also resulted in a significant increase in the nucleus of several N-terminal FAK fragments, the largest of which included the kinase domain but not the focal adhesion targeting domain. This was confirmed using cells that stably expressed recombinant EGFP-FAK. Furthermore, treatment of EGFP-FAK expressing cells with Leptomycin B, an inhibitor of nuclear export, resulted in increased nuclear localisation of EGFP-FAK. Therefore, FAK can shuttle between the nuclear and cytoplasmic compartments and the cellular distribution of N-terminal FAK is regulated by membrane receptor activation.
Jones
Graham
G
Institute for Immunology and Allergy Research, Westmead Millennium Institute, Westmead Hospital, NSW, Australia. graham_jones@wmi.usyd.edu.au
Stewart
Graeme
G
D021581:Active Transport, Cell Nucleus; D000818:Animals; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000276:immunology / Q000378:metabolism*; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D007073:Immunoglobulin E / Q000276:immunology / Q000378:metabolism; D015471:Leukemia, Basophilic, Acute / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008213:Lymphocyte Activation; D011505:Protein-Tyrosine Kinases / Q000276:immunology / Q000378:metabolism*; D051381:Rats; D017455:Receptors, IgE / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction; D014018:Tissue Distribution
D017455:Receptors, IgE; D007073:Immunoglobulin E; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496052:Ptk2 protein, rat