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PMID:15561106

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Citation

Continolo, S, Baruzzi, A, Majeed, M, Caveggion, E, Fumagalli, L, Lowell, CA and Berton, G (2005) The proto-oncogene Fgr regulates cell migration and this requires its plasma membrane localization. Exp. Cell Res. 302:253-69

Abstract

Fgr participates in integrin signaling in myeloid leukocytes. To examine the role of its specific domains in regulating cell migration, we expressed various Fgr molecules in COS-7 cells. Full-length, membrane-bound Fgr, but not an N-terminal truncation mutant that distributed to an intracellular compartment, increased cell migration on fibronectin and enhanced phosphorylation of the p85 subunit of phosphatidylinositol 3-kinase (PI3K), cortactin and focal adhesion kinase (FAK) at Y397 and Y576. Fgr increased Rac GTP loading, and phosphorylation of the Rac GEF Vav2, and bound to a protein complex formed by the Rho inhibitor p190RhoGAP and FAK, increasing p190RhoGAP phosphorylation, in a manner absolutely dependent on membrane localization. A kinase-defective truncation mutant of Fgr increased cell migration, albeit to a much lower extent than full-length Fgr, and was found to associate with the plasma membrane, to activate Rac and to form complexes with p190RhoGAP/FAK. Formation of complexes between p190RhoGAP, Fgr, and the FAK-related protein Pyk2 were also detected in murine macrophages. These findings suggest that the proto-oncogene Fgr regulates cell migration impinging on a signaling pathway implicating FAK/Pyk2 and leading to activation of Rac and the Rho inhibitor p190RhoGAP.

Links

PubMed Online version:10.1016/j.yexcr.2004.09.005

Keywords

Animals; COS Cells; Cell Membrane/metabolism; Cell Movement/physiology; Cercopithecus aethiops; Cortactin; Enzyme Activation; Fibronectins/metabolism; Focal Adhesion Kinase 1; Focal Adhesion Protein-Tyrosine Kinases; Green Fluorescent Proteins/metabolism; Immunoblotting; Macrophages/metabolism; Mice; Microfilament Proteins/metabolism; Microscopy, Confocal; Mutation; Phosphatidylinositol 3-Kinases/metabolism; Phosphorylation; Precipitin Tests; Protein-Tyrosine Kinases/metabolism; Proto-Oncogene Proteins/chemistry; Proto-Oncogene Proteins/genetics; Proto-Oncogene Proteins/physiology; Recombinant Fusion Proteins/metabolism; rac GTP-Binding Proteins/metabolism; rho GTP-Binding Proteins/metabolism; src-Family Kinases

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:FGR

involved_in

GO:0030335: positive regulation of cell migration

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:FGR

involved_in

GO:0018108: peptidyl-tyrosine phosphorylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:FGR

colocalizes_with

GO:0015629: actin cytoskeleton

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:FGR

involved_in

GO:0032956: regulation of actin cytoskeleton organization

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

MOUSE:FGR

colocalizes_with

GO:0032587: ruffle membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:FGR

located_in

GO:0005886: plasma membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:FGR

enables

GO:0004715: non-membrane spanning protein tyrosine kinase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete


See also

References

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