Induction of protein phosphatase type 2A in response to disruption of cell-matrix interactions.
The proliferation of most cells is strictly dependent on cell-matrix interactions, a phenomenon called anchorage dependence. Because tumor cells are often independent of this regulation, it is important to characterize the molecular components that are involved in this control. We therefore investigated a possible role of serine/threonine protein phosphatases in the regulation of anchorage-dependent cell growth. We found that the activity of serine/threonine protein phosphatase type 2A (PP2A) and, to a lesser extent, that of type 1 (PP1), was upregulated in response to the disruption of cellular attachment. In the case of PP2A, this induction was due to the transcriptional activation of the gene and increased expression of its protein. The increase in phosphatase activity corresponded with a decrease in the phosphorylation of cellular proteins that occurred in anchorage-dependent cells, but to a much lesser degree in anchorage-independent cells. At the same time, the activity of cyclin-dependent kinases was downregulated in anchorage-dependent, but not in anchorage-independent cells. Thus, our results indicate that the balance of kinase and phosphatase activity in anchorage-dependent cells is tipped in favor of phosphatase activity, which seems to dominate the extent of reversible protein phosphorylations after cellular detachment. In contrast, anchorage-independent cells appear to neutralize elevated phosphatase activity through sustained, strong kinase activity.
Villalobos Campos
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Department of Molecular Microbiology, School of Medicine, University of Southern California, Los Angeles, California, USA.
Schönthal
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AH
D000818:Animals; D002448:Cell Adhesion; D018929:Cell Culture Techniques; D002453:Cell Cycle; D002460:Cell Line; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D004790:Enzyme Induction; D005109:Extracellular Matrix / Q000378:metabolism*; D007527:Isoenzymes / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D008970:Molecular Weight; D010749:Phosphoprotein Phosphatases / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D011401:Promoter Regions, Genetic / Q000235:genetics; D011506:Proteins / Q000737:chemistry / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014162:Transfection
D007527:Isoenzymes; D011506:Proteins; D012333:RNA, Messenger; D018844:Cyclin-Dependent Kinases; D010749:Phosphoprotein Phosphatases