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PMID:11331870

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Citation

Chen, R, Kim, O, Li, M, Xiong, X, Guan, JL, Kung, HJ, Chen, H, Shimizu, Y and Qiu, Y (2001) Regulation of the PH-domain-containing tyrosine kinase Etk by focal adhesion kinase through the FERM domain. Nat. Cell Biol. 3:439-44

Abstract

Etk/BMX, a member of the Btk family of tyrosine kinases, is highly expressed in cells with great migratory potential, including endothelial cells and metastatic carcinoma cell lines. Here, we present evidence that Etk is involved in integrin signalling and promotes cell migration. The activation of Etk by extracellular matrix proteins is regulated by FAK through an interaction between the PH domain of Etk and the FERM domain of FAK. The lack of Etk activation by extracellular matrix in FAK-null cells could be restored by co-transfection with wild-type FAK. Disrupting the interaction between Etk and FAK diminished the cell migration promoted by either kinase. Furthermore, inhibiting Etk expression in metastatic carcinoma cell lines with an antisense oligonucleotide blocks integrin-mediated migration of these cells. Taken together, our data indicate the essential role of the interaction of the PH domain of Etk and the FERM domain of FAK in integrin signalling.

Links

PubMed Online version:10.1038/35074500

Keywords

Animals; Blotting, Western; COS Cells; Carcinoma/metabolism; Cell Line; Cell Movement; Cells, Cultured; Endothelium, Vascular/cytology; Enzyme Activation; Focal Adhesion Kinase 1; Focal Adhesion Protein-Tyrosine Kinases; Glutathione Transferase/metabolism; Humans; Microscopy, Fluorescence; Oligonucleotides/metabolism; Phosphorylation; Plasmids/metabolism; Precipitin Tests; Protein Binding; Protein Structure, Tertiary; Protein-Tyrosine Kinases/chemistry; Protein-Tyrosine Kinases/metabolism; Recombinant Fusion Proteins/metabolism; Signal Transduction; Time Factors; Transfection; Tumor Cells, Cultured

Significance

Annotations

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

HUMAN:BMX

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q05397

F

Seeded From UniProt

complete

HUMAN:BMX

involved_in

GO:0007165: signal transduction

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:BMX

located_in

GO:0032587: ruffle membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:BMX

enables

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

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:BMX

involved_in

GO:0046777: protein autophosphorylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:FAK1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P51813

F

Seeded From UniProt

complete

HUMAN:FAK1

enables

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

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:FAK1

involved_in

GO:0007229: integrin-mediated signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:FAK1

involved_in

GO:0018108: peptidyl-tyrosine phosphorylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:FAK1

involved_in

GO:0030335: positive regulation of cell migration

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:FAK1

involved_in

GO:0045860: positive regulation of protein kinase activity

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:FAK1

involved_in

GO:0046777: protein autophosphorylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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