The rat tyrosine phosphatase eta increases cell adhesion by activating c-Src through dephosphorylation of its inhibitory phosphotyrosine residue.
The expression of the receptor protein tyrosine phosphatase r-PTPeta is drastically reduced in rat and human malignant thyroid cells, whereas its restoration reverts the neoplastic phenotype of retrovirally transformed rat thyroid cells. Moreover, reduced levels and loss of heterozygosity of DEP-1, the human homolog of r-PTPeta, have been found in many human neoplasias. Here, we report that the r-PTPeta protein binds to c-Src in living cells and dephosphorylates the c-Src inhibitory tyrosine phosphorylation site (Tyr 529), thereby increasing c-Src tyrosine kinase activity in malignant rat thyroid cells stably transfected with r-PTPeta. Tyrosine phosphorylation of focal adhesion kinase (FAK) and paxillin was enhanced in r-PTPeta-expressing cells. This was associated with increased adhesion of malignant r-PTPeta-transfected thyroid cells vs both untransfected cells and cells stably transfected with an inactive r-PTPeta mutant. Treatment of rat thyroid cells with the c-Src inhibitor PP2 decreased cell adhesion to a higher extent in r-PTPeta-transfected cells than in mock-transfected or stably transfected cells with the inactive r-PTPeta mutant, indicating that r-PTPeta regulates cell-substratum adhesion by activating c-Src. Interestingly, the extent of both c-Src dephosphorylation at Tyr 529, FAK and paxillin phosphorylation, and the increased cell adhesion were associated with the degree of r-PTPeta expression.
Pera
Ilaria Le
IL
Department of Experimental and Clinical Medicine, Medical School of Catanzaro, 'Magna Graecia' University of Catanzaro, 88100 Catanzaro, Italy.
Iuliano
Rodolfo
R
Florio
Tullio
T
Susini
Christiane
C
Trapasso
Francesco
F
Santoro
Massimo
M
Chiariotti
Lorenzo
L
Schettini
Gennaro
G
Viglietto
Giuseppe
G
Fusco
Alfredo
A
D000818:Animals; D015153:Blotting, Western; D000081247:CSK Tyrosine-Protein Kinase; D002448:Cell Adhesion; D003598:Cytoskeletal Proteins / Q000378:metabolism; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D009154:Mutation; D009369:Neoplasms / Q000378:metabolism; D051419:Paxillin; D010455:Peptides / Q000737:chemistry; D010641:Phenotype; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000737:chemistry*; D011485:Protein Binding; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry* / Q000378:metabolism* / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D051381:Rats; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3; D013961:Thyroid Gland / Q000166:cytology; D013964:Thyroid Neoplasms / Q000378:metabolism; D014162:Transfection; D014443:Tyrosine / Q000737:chemistry; D019061:src-Family Kinases / Q000378:metabolism
D003598:Cytoskeletal Proteins; C496061:PXN protein, human; D051419:Paxillin; D010455:Peptides; D010750:Phosphoproteins; C496063:Pxn protein, rat; D019000:Phosphotyrosine; D014443:Tyrosine; D005982:Glutathione Transferase; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human; C496052:Ptk2 protein, rat; D019061:src-Family Kinases; C000631346:CSK protein, human; C500747:PTPRJ protein, rat; D017027:Protein Tyrosine Phosphatases; C098066:Ptprj protein, mouse; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3