β1-Integrin and PTEN control the phosphorylation of protein kinase C
| ISSN: | 1470-8728 0264-6021 |
|---|---|
| DOI: | 10.1042/bj3520425 |
| Přístupová URL adresa: | https://explore.openaire.eu/search/publication?articleId=doi_________::36d8d139094039ed1600ad75e213acf5 https://doi.org/10.1042/bj3520425 |
| Rights: | OPEN |
| Přírůstkové číslo: | edsair.doi...........36d8d139094039ed1600ad75e213acf5 |
| Autor: | C P Downes, Davey B. Parekh, N R Leslie, Mike Waterfield, Peter J. Parker, Roy Katso, Katarzyna J. Procyk |
| Rok vydání: | 2000 |
| Předmět: |
Phosphatase
Cell Biology Transfection Biology environment and public health Biochemistry Cell biology enzymes and coenzymes (carbohydrates) Enzyme activator Cell culture Lipid phosphatase activity biology.protein PTEN Phosphorylation biological phenomena cell phenomena and immunity Molecular Biology Protein kinase C |
| Zdroj: | Biochemical Journal. 352:425-433 |
| ISSN: | 1470-8728 0264-6021 |
| DOI: | 10.1042/bj3520425 |
| Popis: | Phosphorylation of protein kinase C (PKC) provides an amplitude control that operates in conjunction with allosteric effectors. Under many conditions, PKC isotypes appear to be highly phosphorylated; however, the cellular inputs that maintain these phosphorylations are not characterized. In the present work, it is shown that there is a differential phosphorylation of PKCdelta in adherent versus suspension cultures of transfected HEK-293 cells. It is established that integrin activation is sufficient to trigger PKCdelta phosphorylation and that this signals through phosphoinositide 3-kinase (PI3-kinase) to stimulate the phosphorylation of two sites, T505 and S662. The loss of signal input to PKCdelta in suspension culture is dependent on the tumour suppressor gene PTEN, which encodes a bi-functional phosphotyrosine/phosphoinositide 3-phosphate phosphatase. In the PTEN(-/-) UM-UC-3 bladder carcinoma cell line grown in suspension, transfected PKCdelta no longer accumulates in a dephospho-form on serum removal. By contrast, in a UM-UC-3-derivative cell line stably expressing PTEN, PKCdelta does become dephosphorylated under these conditions. Employing the PTEN Gly(129)-->Glu mutant, which is selectively defective in lipid phosphatase activity, it was established that it is the lipid phosphatase activity that controls PKCdelta phosphorylation. The evidence indicates that PKCdelta phosphorylation and its latent activity are maintained in serum-deprived adherent cultures through integrin-matrix interactions. This control acts through a pathway involving a lipid product of PI3-kinase in a manner that can be suppressed by PTEN. |
| Databáze: | OpenAIRE |
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