Abstract
Bombesin stimulation of T15 cells in which the inducible N-ras oncogene is overexpressed caused elevated production of inositol phosphates compared to uninduced cells [Wakelam, Davies, Houslay, McKay, Marshall & Hall (1986) Nature (London) 323, 173-176]. This elevated response is shown here to result from increased generation of inositol 1,4,5-trisphosphate leading to an elevated release of intracellular stored Ca2+. Single-cell analysis of Ca2+ release showed that the elevated response is not a consequence of an increased fraction of responding cells. These amplifications are consistent with p21N-ras acting like a guanine nucleotide coupling protein in this cell line.
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- Barbacid M. ras genes. Annu Rev Biochem. 1987;56:779–827. doi: 10.1146/annurev.bi.56.070187.004023. [DOI] [PubMed] [Google Scholar]
- Brown K. D., Blakeley D. M., Hamon M. H., Laurie M. S., Corps A. N. Protein kinase C-mediated negative-feedback inhibition of unstimulated and bombesin-stimulated polyphosphoinositide hydrolysis in Swiss-mouse 3T3 cells. Biochem J. 1987 Aug 1;245(3):631–639. doi: 10.1042/bj2450631. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hancock J. F., Marshall C. J., McKay I. A., Gardner S., Houslay M. D., Hall A., Wakelam M. J. Mutant but not normal p21 ras elevates inositol phospholipid breakdown in two different cell systems. Oncogene. 1988 Aug;3(2):187–193. [PubMed] [Google Scholar]
- Irvine R. F., Anggård E. E., Letcher A. J., Downes C. P. Metabolism of inositol 1,4,5-trisphosphate and inositol 1,3,4-trisphosphate in rat parotid glands. Biochem J. 1985 Jul 15;229(2):505–511. doi: 10.1042/bj2290505. [DOI] [PMC free article] [PubMed] [Google Scholar]
- McGrath J. P., Capon D. J., Goeddel D. V., Levinson A. D. Comparative biochemical properties of normal and activated human ras p21 protein. Nature. 1984 Aug 23;310(5979):644–649. doi: 10.1038/310644a0. [DOI] [PubMed] [Google Scholar]
- McKay I. A., Marshall C. J., Calés C., Hall A. Transformation and stimulation of DNA synthesis in NIH-3T3 cells are a titratable function of normal p21N-ras expression. EMBO J. 1986 Oct;5(10):2617–2621. doi: 10.1002/j.1460-2075.1986.tb04542.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Palmer S., Hughes K. T., Lee D. Y., Wakelam M. J. Development of a novel, Ins(1,4,5)P3-specific binding assay. Its use to determine the intracellular concentration of Ins(1,4,5)P3 in unstimulated and vasopressin-stimulated rat hepatocytes. Cell Signal. 1989;1(2):147–156. doi: 10.1016/0898-6568(89)90004-1. [DOI] [PubMed] [Google Scholar]
- Pollock W. K., Rink T. J., Irvine R. F. Liberation of [3H]arachidonic acid and changes in cytosolic free calcium in fura-2-loaded human platelets stimulated by ionomycin and collagen. Biochem J. 1986 May 1;235(3):869–877. doi: 10.1042/bj2350869. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Swann K., Whitaker M. The part played by inositol trisphosphate and calcium in the propagation of the fertilization wave in sea urchin eggs. J Cell Biol. 1986 Dec;103(6 Pt 1):2333–2342. doi: 10.1083/jcb.103.6.2333. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tanabe T., Nukada T., Nishikawa Y., Sugimoto K., Suzuki H., Takahashi H., Noda M., Haga T., Ichiyama A., Kangawa K. Primary structure of the alpha-subunit of transducin and its relationship to ras proteins. Nature. 1985 May 16;315(6016):242–245. doi: 10.1038/315242a0. [DOI] [PubMed] [Google Scholar]
- Tsien R. Y. New calcium indicators and buffers with high selectivity against magnesium and protons: design, synthesis, and properties of prototype structures. Biochemistry. 1980 May 27;19(11):2396–2404. doi: 10.1021/bi00552a018. [DOI] [PubMed] [Google Scholar]
- Wakelam M. J., Davies S. A., Houslay M. D., McKay I., Marshall C. J., Hall A. Normal p21N-ras couples bombesin and other growth factor receptors to inositol phosphate production. Nature. 1986 Sep 11;323(6084):173–176. doi: 10.1038/323173a0. [DOI] [PubMed] [Google Scholar]
- Wakelam M. J. Inhibition of the amplified bombesin-stimulated inositol phosphate response in N-ras transformed cells by high density culturing. FEBS Lett. 1988 Feb 8;228(1):182–186. doi: 10.1016/0014-5793(88)80613-6. [DOI] [PubMed] [Google Scholar]
- Willingham M. C., Banks-Schlegel S. P., Pastan I. H. Immunocytochemical localization in normal and transformed human cells in tissue culture using a monoclonal antibody to the src protein of the Harvey strain of murine sarcoma virus. Exp Cell Res. 1983 Nov;149(1):141–149. doi: 10.1016/0014-4827(83)90387-7. [DOI] [PubMed] [Google Scholar]