Skip Navigation

This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Request Permissions
Google Scholar
Right arrow Articles by Ishijima, S.
Right arrow Articles by Tatibana, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ishijima, S.
Right arrow Articles by Tatibana, M.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

J. Biochem, 1988, Vol. 104, No. 4 570-575
© 1988 Japanese Biochemical Society

research-article

Evidence for Early Mitogenic Stimulation of Metabolic Flux through Phosphoribosyl Pyrophosphate into Nucleotides in Swiss 3T3 Cells1

Sumio Ishijima, Kazuko Kita, Nobuhiro Kinoshita2, Toshiharu Ishizuka, Nobuo Suzuki and Masamiti Tatibana1

Department of Biochemistry, Chiba University School of Medicine Chiba, Chiba 280

3To whom correspondence should be addressed

Various mitogens activate purine and pyrimidine de novo biosynthesis and purine base phosphoribosylation as an early response in quiescent fibroblasts. Increased synthesis of 5-phosphoribosyl 1-pyrophosphate (PRPP) may precede or underlie these activations, but little direct evidence has been presented for this notion, due to lack of suitable analytical methods. To preferentially label intracellular ribose phosphate and quantitatively follow metabolic flux through PRPP into nucleotides, we prepared [ribosyl-14C]inosine and used it as a tracer. Evidence showed the validity of this method. Prior exposure of quiescent Swiss 3T3 cells in culture to epidermal growth factor plus insulin for 45–60 min enhanced approximately 2-fold the radioactivity incorporation from [ribosyl-14C]inosine into nucleotides, without increasing the specific radioactivity of intracellular free ribose 5-phosphate. [14C]Uracil incorporation into nucleotides, a measure of PRPP-independent ribose phosphate utilization for nucleotide synthesis, was not increased. These and other results indicate that epidermal growth factor plus insulin stimulates the metabolic flux through PRPP. Similar extents of stimulation were induced by bombesin and melittin in combination with insulin and by fibroblast growth factor alone, suggesting the presence of an unknown signaling pathway common to these mitogens. This system is highly useful for studies of the mechanisms that stimulate in situ activity of PRPP synthetase.

1This study was supported in part by Grants-in-Aid from the Ministries of Education, Science and Culture (61440030) and of Health and Welfare of Japan.

2Present address: Research Center, Nisshin Flour Milling Co., Iruma, Saitama 354.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 EndocrinologyHome page
S. Metz, S. Holland, L. Johnson, E. Espling, M. Rabaglia, V. Segu, J. S. Brockenbrough, and P. O. Tran
Inosine-5'-Monophosphate Dehydrogenase Is Required for Mitogenic Competence of Transformed Pancreatic {beta} Cells
Endocrinology, January 1, 2001; 142(1): 193 - 204.
[Abstract] [Full Text] [PDF]

Home page
 JPEN J Parenter Enteral NutrHome page
T. Chikenji, M. Mizutani, H. Furukawa, and Y. Kitsukawa
Stimulation of Protein, RNA, and Nucleotide Synthesis in Lymphocytes After Abdominal Surgery Is Not Affected by Postoperative Amino Acid Supply
JPEN J Parenter Enteral Nutr, July 1, 1991; 15(4): 371 - 375.
[Abstract] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.