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Transforming protein of avian sarcoma virus UR2 is associated with phosphatidylinositol kinase activity: possible role in tumorigenesis

Journal Article · · Proc. Natl. Acad. Sci. U.S.A.; (United States)
; ;
The transforming protein of avian sarcoma virus UR2, p68/sup v-ros/, has an associated tyrosine-specific protein kinase activity similar to that of p60/sup v-src/ and several other oncogene products. However, this activity has not been linked unequivocally to transformation, and the physiological action of these proteins remains in doubt. It has now been found that immunoprecipitated p68/sup v-ros/ also is associated with phosphatidylinositol (PtdIns) kinase activity. PtdIns 4,5-bisphosphate (PtdIns(4,5)P/sub 2/) specifically inhibits both this activity and the autophosphorylation of p68/sup v-ros/. Moreover, cells transformed by UR2 showed significant increases in /sup 32/P-labeling of PtdIns 4-phosphate (PtdIns4P) and PtdIns(4,5)P/sub 2/ and in the formation of their catabolites, inositol 1,4-bisphosphate and inositol 1,4,5-trisphosphate, as compared to uninfected cells. These results suggest that a physiologically relevant function of oncogene kinases might be the phosphorylation of PtdIns and that increased turnover of PtdIns4P and PtdIns(4,5)P/sub 2/ might play a role in transformation by increasing the formation of diacylglycerol, a catabolite of polyphosphoinositides that activates kinase C. This protein copurifies with the phorbol ester receptor, and its activation is likely to be intimately linked with mitogenesis. This hypothesis suggests a mechanisms whereby certain oncogene proteins might cause the unrestricted growth typical of transformed cells and could explain why tumor promoters mimic many of the effects of transformation. 41 references, 5 figures, 3 tables.
Research Organization:
Univ. of Rochester, NY
OSTI ID:
6194219
Journal Information:
Proc. Natl. Acad. Sci. U.S.A.; (United States), Journal Name: Proc. Natl. Acad. Sci. U.S.A.; (United States) Vol. 81; ISSN PNASA
Country of Publication:
United States
Language:
English

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Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIRDS
CARBOHYDRATES
CELL TRANSFORMATIONS
CHEMICAL REACTIONS
CHICKENS
DATA
DAYS LIVING RADIOISOTOPES
DISEASES
ENZYME ACTIVITY
ENZYMES
EXPERIMENTAL DATA
FOWL
INFORMATION
INOSITOL
INOSITOLS
ISOTOPE APPLICATIONS
ISOTOPES
LABELLED COMPOUNDS
LABELLING
LIGHT NUCLEI
MICROORGANISMS
MONOSACCHARIDES
NEOPLASMS
NUCLEI
NUMERICAL DATA
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
OXYGEN COMPOUNDS
PARASITES
PHOSPHATES
PHOSPHORUS 32
PHOSPHORUS COMPOUNDS
PHOSPHORUS ISOTOPES
PHOSPHORUS-GROUP TRANSFERASES
PHOSPHORYLATION
PHOSPHOTRANSFERASES
PROMOTERS
PROTEINS
RADIOISOTOPES
SACCHARIDES
SARCOMAS
TRACER TECHNIQUES
TRANSFERASES
TUMOR PROMOTERS
VERTEBRATES
VIRUSES