title: Neurofibromin physically interacts with the N-terminal domain of focal adhesion kinase.
abstract: The NF1 gene that is altered in patients with type 1 neurofibromatosis (NF1) encodes a neurofibromin protein that functions as a tumor suppressor. In this report, we show for the first time physical interaction between neurofibromin and focal adhesion kinase (FAK), the protein that localizes at focal adhesions. We show that neurofibromin associates with the N-terminal domain of FAK, and that the C-terminal domain of neurofibromin directly interacts with FAK. Confocal microscopy demonstrates colocalization of NF1 and FAK in the cytoplasm, perinuclear and nuclear regions inside the cells. Nf1+/+ MEF cells expressed less cell growth during serum deprivation conditions, and adhered less on collagen and fibronectin-treated plates than Nf1(-/-) MEF cells, associated with changes in actin and FAK staining. In addition, Nf1+/+ MEF cells detached more significantly than Nf1(-/-) MEF cells by disruption of FAK signaling with the dominant-negative inhibitor of FAK, C-terminal domain of FAK (FAK-CD). Thus, the results demonstrate the novel interaction of neurofibromin and FAK and suggest their involvement in cell adhesion, cell growth, and other cellular events and pathways.
authors.affiliation: University of Florida Shands Cancer Center, Gainesville, Florida, USA.
authors.forename: Frederick
authors.initials: F
authors.lastname: Kweh
authors.forename: Min
authors.initials: M
authors.lastname: Zheng
authors.forename: Elena
authors.initials: E
authors.lastname: Kurenova
authors.forename: Margaret
authors.initials: M
authors.lastname: Wallace
authors.forename: Vita
authors.initials: V
authors.lastname: Golubovskaya
authors.forename: William G
authors.initials: WG
authors.lastname: Cance
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D002448:Cell Adhesion; D002460:Cell Line; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000737:chemistry / Q000378:metabolism*; D047468:Immunoprecipitation; D051379:Mice; D018613:Microscopy, Confocal; D025542:Neurofibromin 1 / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding
chemical_list: D025542:Neurofibromin 1; D051416:Focal Adhesion Protein-Tyrosine Kinases