Phosphatidylinositol turnover and transformation of cells by Abelson murine leukaemia virus.

Fry, Michael; Gebhardt, Angelika; Parker, Peter J.; Foulkes, J G

doi:10.1002/j.1460-2075.1985.tb04061.x

Cited by 55 publications

(18 citation statements)

References 56 publications

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“…Three cAMP-independent kinases can phosphorylate five sites. These include protease-activated kinase 11 (12,31) and protein kinase C, a Ca2+-activated kinase which may also be phospholipid dependent (11,29), both of which seem to have a fairly broad substrate spectrum. Finally, several laboratories have recently purified a kinase which is apparently specific for S6 and distinct from the kinases described above by a number of criteria (3,10,27,38).…”

Section: Resultsmentioning

confidence: 99%

Phosphorylation of the Saccharomyces cerevisiae equivalent of ribosomal protein S6 has no detectable effect on growth.

Johnson¹,

Warner²

1987

Mol. Cell. Biol.

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The phosphorylation of mammalian ribosomal protein S6 is affected by a variety of agents, including growth factors and tumor promoters, as well as by expressed oncogenes. Its potential role in the regulation of protein synthesis has been the object of much study. We have developed strains of Saccharomyces cerevisiae in which the phosphorylatable serines of the equivalent ribosomal protein (S10) were converted to alanines by site-directed mutagenesis. The S10 of such cells is not phosphorylated. Comparison of these cells with the parental cells, whose genomes differ by only six nucleotides, revealed no differences in the lag phase or logarithmic phase of a growth cycle, in growth on different carbon sources, in sporulation, or in sensitivity to heat shock. We conclude that in S. cerevisiae the phosphorylation of ribosomal protein S10 may play no role in regulating the synthesis of proteins. This conclusion leads one to ask whether certain protein phosphorylations are simply the adventitious, if easily observable, result of the imperfect specificity of one or another protein kinase.Ribosomal protein S6 is the major phosphoprotein of eucaryotic ribosomes. It can be phosphorylated at multiple sites (two in Saccharomyces cerevisiae and at least five in vertebrates), and the degree of phosphorylation is somehow related to cell proliferation. A variety of stimuli and agents have been observed to affect the phosphorylation of S6, including insulin (35,40,44), growth factors (40), serum treatment (40), viral transformation (7), phorbol esters (3), and fertilization (2, 26). Phosphorylation of the S6 protein is carried out by a number of kinases, one of which is apparently specific for S6, and is activated by at least two regulatory mechanisms (4).In S. cerevisiae the homologous ribosomal protein, referred to as S10, is phosphorylated after transfer of a stationary culture to fresh nutrient medium (16). Phosphorylation also occurs at an early stage of germination (37). As in other eucaryotes, the protein is dephosphorylated during heat shock (16).At present, much is known about the phenomenology of S6 phosphorylation, but little about its function. Generally, as phosphorylation of protein S6 increases, the level of protein synthesis increases (14, 40), and as dephosphorylation of S6 occurs, the level of protein synthesis decreases (13, 34). However, phosphorylation of S6 has been observed to be stimulated under conditions in which protein synthesis increased, decreased, or remained unchanged (14,17,41). In serum-stimulated 3T3 cells, ribosomes containing highly phosphorylated S6 are preferentially incorporated into new polysomes, suggesting a role in mRNA recruitment (8,40). Such a role is supported by the localization of S6 in the mRNA-binding site of 80S ribosomes (39). In vitro attempts to demonstrate an effect of S6 phosphorylation have been successful in some cases (6) and unsuccessful in others (20,25).Because of the potential importance of the phosphorylation of S6 to the regulation of cell growth and because of th...

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Section: Resultsmentioning

confidence: 99%

Phosphorylation of the Saccharomyces cerevisiae equivalent of ribosomal protein S6 has no detectable effect on growth.

Johnson¹,

Warner²

1987

Mol. Cell. Biol.

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“…PtdIns kinase activities have been reported to be associated with several tyrosine kinase activities including the EGF receptor/kinase (28), the insulin receptor/kinase (25,28), pp60v-src (26), pp68vr-s (27), and the Abelson gene product (34 …”

Section: Discussionmentioning

confidence: 99%

Phosphatidylinositol kinase is activated in membranes derived from cells treated with epidermal growth factor.

Walker

Pike

1987

Proc. Natl. Acad. Sci. U.S.A.

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The ability of epidermal growth factor (EGF) to stimulate phosphatidylinositol (PtdIns) kinase activity in A431 cells was examined. The incorporation of 32p from [y-32P]ATP into PtdIns by A431 membranes was increased in membranes prepared from cells that had been pretreated with EGF. Demonstration of a stimulation of the PtdIns kinase activity by EGF required the use of subconfluent cultures and was dependent on the inclusion of protease inhibitors in the buffers used to prepare the membranes. Stimulation of the PtdIns kinase activity was rapid. The activation peaked 2 min after the addition of EGF and declined slowly thereafter. Half-maximal stimulation of the PtdIns kinase occurred at 7 nM EGF. Kinetic analyses of the reaction indicated that treatment of the cells with EGF resulted in a decrease in the Km for PtdIns with no change in the V... The kinetic parameters for the utilization of ATP were unchanged in the EGF-treated membranes compared to the control membranes. Pretreatment of the cells with the phorbol ester phorbol 12-myristate 13-acetate blocked the ability of EGF to stimulate PtdIns kinase activity. These findings demonstrate that a PtdIns kinase activity in A431 cells is regulated by EGF and provide a good system for examining the mechanism by which EGF stimulates the activity of this intracellular enzyme.

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“…The v-abl kinase activity in cell extracts was determined as described previously Fry et al, 1985). Two-dimensional phosphoamino acid analysis was performed by the method of Hunter and Sefton (1980).…”

Section: Methodsmentioning

confidence: 99%

Abelson transformed fibroblasts lacking the EGF receptor are not tumourigenic in nude mice.

Gebhardt¹,

Bell²,

Foulkes³

1986

The EMBO Journal

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Phosphatidylinositol turnover and transformation of cells by Abelson murine leukaemia virus.

Cited by 55 publications

References 56 publications

Phosphorylation of the Saccharomyces cerevisiae equivalent of ribosomal protein S6 has no detectable effect on growth.

Phosphorylation of the Saccharomyces cerevisiae equivalent of ribosomal protein S6 has no detectable effect on growth.

Phosphatidylinositol kinase is activated in membranes derived from cells treated with epidermal growth factor.

Abelson transformed fibroblasts lacking the EGF receptor are not tumourigenic in nude mice.

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