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. 1993 Apr 2;121(2):409–422. doi: 10.1083/jcb.121.2.409

Effect of nerve growth factor and fibroblast growth factor on PC12 cells: inhibition by orthovanadate

PMCID: PMC2200105  PMID: 8468355

Abstract

Sodium orthovanadate, an inhibitor of protein tyrosine phosphatases, causes increased levels of tyrosine phosphorylation and blocks, at noncytotoxic concentrations, the differentiative response of rat pheochromocytoma (PC12) cells to beta-nerve growth factor (beta NGF) and basic fibroblast growth factor (bFGF) in a reversible manner. It also prevents growth factor-induced neurite proliferation in primed cells and causes the retraction of previously formed neurites, even in the presence of beta NGF or bFGF. It is equally effective in blocking neurite proliferation by 8-Br-cAMP. Zinc chloride and ammonium molybdate, two other inhibitors of tyrosine phosphatases, also cause parallel decreases in neurite proliferation. Orthovanadate generally reduces the transcription of immediate early response genes (TIS 8 and c-fos) and secondary response genes (ornithine decarboxylase (ODC), acetyl-cholinesterase (AChE) and SCG 10) induced by beta NGF, bFGF, EGF, and PMA, albeit in a variable fashion. There was no observed effect on the kinetics of expression as judged by TIS 8 induction by beta NGF and protein kinase C (PKC) downregulation did not change the levels of inhibition by orthovanadate seen in control cells. Orthovanadate does not affect the production of diacylglycerol induced by beta NGF or bFGF. These observations are consistent with the view that growth factor stimulation of differentiation in PC12 cells involves at least one other PKC independent pathway, and that cAMP and PMA (and their active analogs) activate tyrosine kinases (albeit probably secondarily), which are at least partially responsible for their actions. Although the exact site(s) of action of orthovanadate that lead to the inhibition of growth factor-induced neurite proliferation are unknown, the results presented suggest that it prolongs tyrosine phosphorylations by nonreceptor tyrosine kinases that act downstream from the receptor kinases.

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Selected References

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  1. AMES B. N., DUBIN D. T. The role of polyamines in the neutralization of bacteriophage deoxyribonucleic acid. J Biol Chem. 1960 Mar;235:769–775. [PubMed] [Google Scholar]
  2. Alemà S., Casalbore P., Agostini E., Tatò F. Differentiation of PC12 phaeochromocytoma cells induced by v-src oncogene. Nature. 1985 Aug 8;316(6028):557–559. doi: 10.1038/316557a0. [DOI] [PubMed] [Google Scholar]
  3. Altin J. G., Bradshaw R. A. Production of 1,2-diacylglycerol in PC12 cells by nerve growth factor and basic fibroblast growth factor. J Neurochem. 1990 May;54(5):1666–1676. doi: 10.1111/j.1471-4159.1990.tb01220.x. [DOI] [PubMed] [Google Scholar]
  4. Altin J. G., Kujubu D. A., Raffioni S., Eveleth D. D., Herschman H. R., Bradshaw R. A. Differential induction of primary-response (TIS) genes in PC12 pheochromocytoma cells and the unresponsive variant PC12nnr5. J Biol Chem. 1991 Mar 25;266(9):5401–5406. [PubMed] [Google Scholar]
  5. Anderson N. G., Maller J. L., Tonks N. K., Sturgill T. W. Requirement for integration of signals from two distinct phosphorylation pathways for activation of MAP kinase. Nature. 1990 Feb 15;343(6259):651–653. doi: 10.1038/343651a0. [DOI] [PubMed] [Google Scholar]
  6. BLIGH E. G., DYER W. J. A rapid method of total lipid extraction and purification. Can J Biochem Physiol. 1959 Aug;37(8):911–917. doi: 10.1139/o59-099. [DOI] [PubMed] [Google Scholar]
  7. Bar-Sagi D., Feramisco J. R. Microinjection of the ras oncogene protein into PC12 cells induces morphological differentiation. Cell. 1985 Oct;42(3):841–848. doi: 10.1016/0092-8674(85)90280-6. [DOI] [PubMed] [Google Scholar]
  8. Bothwell M. Keeping track of neurotrophin receptors. Cell. 1991 Jun 14;65(6):915–918. doi: 10.1016/0092-8674(91)90540-f. [DOI] [PubMed] [Google Scholar]
  9. Boulton T. G., Nye S. H., Robbins D. J., Ip N. Y., Radziejewska E., Morgenbesser S. D., DePinho R. A., Panayotatos N., Cobb M. H., Yancopoulos G. D. ERKs: a family of protein-serine/threonine kinases that are activated and tyrosine phosphorylated in response to insulin and NGF. Cell. 1991 May 17;65(4):663–675. doi: 10.1016/0092-8674(91)90098-j. [DOI] [PubMed] [Google Scholar]
  10. Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1006/abio.1976.9999. [DOI] [PubMed] [Google Scholar]
  11. Brautigan D. L., Pinault F. M. Activation of membrane protein-tyrosine phosphatase involving cAMP- and Ca2+/phospholipid-dependent protein kinases. Proc Natl Acad Sci U S A. 1991 Aug 1;88(15):6696–6700. doi: 10.1073/pnas.88.15.6696. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Brown D. J., Gordon J. A. The stimulation of pp60v-src kinase activity by vanadate in intact cells accompanies a new phosphorylation state of the enzyme. J Biol Chem. 1984 Aug 10;259(15):9580–9586. [PubMed] [Google Scholar]
  13. Cantley L. C., Auger K. R., Carpenter C., Duckworth B., Graziani A., Kapeller R., Soltoff S. Oncogenes and signal transduction. Cell. 1991 Jan 25;64(2):281–302. doi: 10.1016/0092-8674(91)90639-g. [DOI] [PubMed] [Google Scholar]
  14. Cantley L. C., Jr, Resh M. D., Guidotti G. Vanadate inhibits the red cell (Na+, K+) ATPase from the cytoplasmic side. Nature. 1978 Apr 6;272(5653):552–554. doi: 10.1038/272552a0. [DOI] [PubMed] [Google Scholar]
  15. Cartwright C. A., Eckhart W., Simon S., Kaplan P. L. Cell transformation by pp60c-src mutated in the carboxy-terminal regulatory domain. Cell. 1987 Apr 10;49(1):83–91. doi: 10.1016/0092-8674(87)90758-6. [DOI] [PubMed] [Google Scholar]
  16. Cassel D., Zhuang Y. X., Glaser L. Vanadate stimulates Na+/H+ exchange activity in A431 cells. Biochem Biophys Res Commun. 1984 Jan 30;118(2):675–681. doi: 10.1016/0006-291x(84)91356-1. [DOI] [PubMed] [Google Scholar]
  17. Chijiwa T., Mishima A., Hagiwara M., Sano M., Hayashi K., Inoue T., Naito K., Toshioka T., Hidaka H. Inhibition of forskolin-induced neurite outgrowth and protein phosphorylation by a newly synthesized selective inhibitor of cyclic AMP-dependent protein kinase, N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide (H-89), of PC12D pheochromocytoma cells. J Biol Chem. 1990 Mar 25;265(9):5267–5272. [PubMed] [Google Scholar]
  18. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  19. Contreras M. L., Guroff G. Calcium-dependent nerve growth factor-stimulated hydrolysis of phosphoinositides in PC12 cells. J Neurochem. 1987 May;48(5):1466–1472. doi: 10.1111/j.1471-4159.1987.tb05687.x. [DOI] [PubMed] [Google Scholar]
  20. Cooper J. A., Gould K. L., Cartwright C. A., Hunter T. Tyr527 is phosphorylated in pp60c-src: implications for regulation. Science. 1986 Mar 21;231(4744):1431–1434. doi: 10.1126/science.2420005. [DOI] [PubMed] [Google Scholar]
  21. Cremins J., Wagner J. A., Halegoua S. Nerve growth factor action is mediated by cyclic AMP- and Ca+2/phospholipid-dependent protein kinases. J Cell Biol. 1986 Sep;103(3):887–893. doi: 10.1083/jcb.103.3.887. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Curran T., Peters G., Van Beveren C., Teich N. M., Verma I. M. FBJ murine osteosarcoma virus: identification and molecular cloning of biologically active proviral DNA. J Virol. 1982 Nov;44(2):674–682. doi: 10.1128/jvi.44.2.674-682.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Damon D. H., D'Amore P. A., Wagner J. A. Nerve growth factor and fibroblast growth factor regulate neurite outgrowth and gene expression in PC12 cells via both protein kinase C- and cAMP-independent mechanisms. J Cell Biol. 1990 Apr;110(4):1333–1339. doi: 10.1083/jcb.110.4.1333. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Djurhuus R. Ornithine decarboxylase (EC 4.1.1.17) assay based upon the retention of putrescine by a strong cation-exchange paper. Anal Biochem. 1981 May 15;113(2):352–355. doi: 10.1016/0003-2697(81)90088-9. [DOI] [PubMed] [Google Scholar]
  25. Dubyak G. R., Kleinzeller A. The insulin-mimetic effects of vanadate in isolated rat adipocytes. Dissociation from effects of vanadate as a (Na+-K+)ATPase inhibitor. J Biol Chem. 1980 Jun 10;255(11):5306–5312. [PubMed] [Google Scholar]
  26. Dunphy W. G., Kumagai A. The cdc25 protein contains an intrinsic phosphatase activity. Cell. 1991 Oct 4;67(1):189–196. doi: 10.1016/0092-8674(91)90582-j. [DOI] [PubMed] [Google Scholar]
  27. English L. H., Macara I. G., Cantley L. C. Vanadium stimulates the (Na+,K+) pump in friend erythroleukemia cells and blocks erythropoiesis. J Cell Biol. 1983 Oct;97(4):1299–1302. doi: 10.1083/jcb.97.4.1299. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Eveleth D. D., Hanecak R., Fox G. M., Fan H., Bradshaw R. A. v-src genes stimulate neurite outgrowth in pheochromocytoma (PC12) variants unresponsive to neurotrophic factors. J Neurosci Res. 1989 Sep;24(1):67–71. doi: 10.1002/jnr.490240110. [DOI] [PubMed] [Google Scholar]
  29. Federoff H. J., Grabczyk E., Fishman M. C. Dual regulation of GAP-43 gene expression by nerve growth factor and glucocorticoids. J Biol Chem. 1988 Dec 25;263(36):19290–19295. [PubMed] [Google Scholar]
  30. Feinstein S. C., Dana S. L., McConlogue L., Shooter E. M., Coffino P. Nerve growth factor rapidly induces ornithine decarboxylase mRNA in PC12 rat pheochromocytoma cells. Proc Natl Acad Sci U S A. 1985 Sep;82(17):5761–5765. doi: 10.1073/pnas.82.17.5761. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Fox G. M., Schiffer S. G., Rohde M. F., Tsai L. B., Banks A. R., Arakawa T. Production, biological activity, and structure of recombinant basic fibroblast growth factor and an analog with cysteine replaced by serine. J Biol Chem. 1988 Dec 5;263(34):18452–18458. [PubMed] [Google Scholar]
  32. Frazier W. A., Ohlendorf C. E., Boyd L. F., Aloe L., Johnson E. M., Ferrendelli J. A., Bradshaw R. A. Mechanism of action of nerve growth factor and cyclic AMP on neurite outgrowth in embryonic chick sensory ganglia: demonstration of independent pathways of stimulation. Proc Natl Acad Sci U S A. 1973 Aug;70(8):2448–2452. doi: 10.1073/pnas.70.8.2448. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Friesel R., Burgess W. H., Maciag T. Heparin-binding growth factor 1 stimulates tyrosine phosphorylation in NIH 3T3 cells. Mol Cell Biol. 1989 May;9(5):1857–1865. doi: 10.1128/mcb.9.5.1857. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Gautier J., Solomon M. J., Booher R. N., Bazan J. F., Kirschner M. W. cdc25 is a specific tyrosine phosphatase that directly activates p34cdc2. Cell. 1991 Oct 4;67(1):197–211. doi: 10.1016/0092-8674(91)90583-k. [DOI] [PubMed] [Google Scholar]
  35. Ginty D. D., Glowacka D., DeFranco C., Wagner J. A. Nerve growth factor-induced neuronal differentiation after dominant repression of both type I and type II cAMP-dependent protein kinase activities. J Biol Chem. 1991 Aug 15;266(23):15325–15333. [PubMed] [Google Scholar]
  36. Glowacka D., Wagner J. A. Role of the cAMP-dependent protein kinase and protein kinase C in regulating the morphological differentiation of PC12 cells. J Neurosci Res. 1990 Apr;25(4):453–462. doi: 10.1002/jnr.490250403. [DOI] [PubMed] [Google Scholar]
  37. Goldschmidt-Clermont P. J., Kim J. W., Machesky L. M., Rhee S. G., Pollard T. D. Regulation of phospholipase C-gamma 1 by profilin and tyrosine phosphorylation. Science. 1991 Mar 8;251(4998):1231–1233. doi: 10.1126/science.1848725. [DOI] [PubMed] [Google Scholar]
  38. Greene L. A., McGuire J. C. Induction of ornithine decarboxylase by nerve growth factor dissociated from effects on survival and neurite outgrowth. Nature. 1978 Nov 9;276(5684):191–194. doi: 10.1038/276191a0. [DOI] [PubMed] [Google Scholar]
  39. Greene L. A., Rein G. Synthesis, storage and release of acetylcholine by a noradrenergic pheochromocytoma cell line. Nature. 1977 Jul 28;268(5618):349–351. doi: 10.1038/268349a0. [DOI] [PubMed] [Google Scholar]
  40. Greene L. A., Rukenstein A. Regulation of acetylcholinesterase activity by nerve growth factor. Role of transcription and dissociation from effects on proliferation and neurite outgrowth. J Biol Chem. 1981 Jun 25;256(12):6363–6367. [PubMed] [Google Scholar]
  41. Greene L. A., Tischler A. S. Establishment of a noradrenergic clonal line of rat adrenal pheochromocytoma cells which respond to nerve growth factor. Proc Natl Acad Sci U S A. 1976 Jul;73(7):2424–2428. doi: 10.1073/pnas.73.7.2424. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Gómez N., Cohen P. Dissection of the protein kinase cascade by which nerve growth factor activates MAP kinases. Nature. 1991 Sep 12;353(6340):170–173. doi: 10.1038/353170a0. [DOI] [PubMed] [Google Scholar]
  43. Heasley L. E., Johnson G. L. Regulation of protein kinase C by nerve growth factor, epidermal growth factor, and phorbol esters in PC12 pheochromocytoma cells. J Biol Chem. 1989 May 25;264(15):8646–8652. [PubMed] [Google Scholar]
  44. Hempstead B. L., Martin-Zanca D., Kaplan D. R., Parada L. F., Chao M. V. High-affinity NGF binding requires coexpression of the trk proto-oncogene and the low-affinity NGF receptor. Nature. 1991 Apr 25;350(6320):678–683. doi: 10.1038/350678a0. [DOI] [PubMed] [Google Scholar]
  45. Herschman H. R. Primary response genes induced by growth factors and tumor promoters. Annu Rev Biochem. 1991;60:281–319. doi: 10.1146/annurev.bi.60.070191.001433. [DOI] [PubMed] [Google Scholar]
  46. Johnson D., Lanahan A., Buck C. R., Sehgal A., Morgan C., Mercer E., Bothwell M., Chao M. Expression and structure of the human NGF receptor. Cell. 1986 Nov 21;47(4):545–554. doi: 10.1016/0092-8674(86)90619-7. [DOI] [PubMed] [Google Scholar]
  47. Kaplan D. R., Hempstead B. L., Martin-Zanca D., Chao M. V., Parada L. F. The trk proto-oncogene product: a signal transducing receptor for nerve growth factor. Science. 1991 Apr 26;252(5005):554–558. doi: 10.1126/science.1850549. [DOI] [PubMed] [Google Scholar]
  48. Kaplan D. R., Martin-Zanca D., Parada L. F. Tyrosine phosphorylation and tyrosine kinase activity of the trk proto-oncogene product induced by NGF. Nature. 1991 Mar 14;350(6314):158–160. doi: 10.1038/350158a0. [DOI] [PubMed] [Google Scholar]
  49. Kazlauskas A., Cooper J. A. Protein kinase C mediates platelet-derived growth factor-induced tyrosine phosphorylation of p42. J Cell Biol. 1988 Apr;106(4):1395–1402. doi: 10.1083/jcb.106.4.1395. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Kim U. H., Fink D., Jr, Kim H. S., Park D. J., Contreras M. L., Guroff G., Rhee S. G. Nerve growth factor stimulates phosphorylation of phospholipase C-gamma in PC12 cells. J Biol Chem. 1991 Jan 25;266(3):1359–1362. [PubMed] [Google Scholar]
  51. Klein R., Jing S. Q., Nanduri V., O'Rourke E., Barbacid M. The trk proto-oncogene encodes a receptor for nerve growth factor. Cell. 1991 Apr 5;65(1):189–197. doi: 10.1016/0092-8674(91)90419-y. [DOI] [PubMed] [Google Scholar]
  52. Kmiecik T. E., Shalloway D. Activation and suppression of pp60c-src transforming ability by mutation of its primary sites of tyrosine phosphorylation. Cell. 1987 Apr 10;49(1):65–73. doi: 10.1016/0092-8674(87)90756-2. [DOI] [PubMed] [Google Scholar]
  53. Kremer N. E., D'Arcangelo G., Thomas S. M., DeMarco M., Brugge J. S., Halegoua S. Signal transduction by nerve growth factor and fibroblast growth factor in PC12 cells requires a sequence of src and ras actions. J Cell Biol. 1991 Nov;115(3):809–819. doi: 10.1083/jcb.115.3.809. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Kujubu D. A., Lim R. W., Varnum B. C., Herschman H. R. Induction of transiently expressed genes in PC-12 pheochromocytoma cells. Oncogene. 1987;1(3):257–262. [PubMed] [Google Scholar]
  55. Lau K. H., Tanimoto H., Baylink D. J. Vanadate stimulates bone cell proliferation and bone collagen synthesis in vitro. Endocrinology. 1988 Dec;123(6):2858–2867. doi: 10.1210/endo-123-6-2858. [DOI] [PubMed] [Google Scholar]
  56. Levi A., Alemà S. The mechanism of action of nerve growth factor. Annu Rev Pharmacol Toxicol. 1991;31:205–228. doi: 10.1146/annurev.pa.31.040191.001225. [DOI] [PubMed] [Google Scholar]
  57. Lim R. W., Varnum B. C., Herschman H. R. Cloning of tetradecanoyl phorbol ester-induced 'primary response' sequences and their expression in density-arrested Swiss 3T3 cells and a TPA non-proliferative variant. Oncogene. 1987;1(3):263–270. [PubMed] [Google Scholar]
  58. Lindenbaum M. H., Carbonetto S., Grosveld F., Flavell D., Mushynski W. E. Transcriptional and post-transcriptional effects of nerve growth factor on expression of the three neurofilament subunits in PC-12 cells. J Biol Chem. 1988 Apr 25;263(12):5662–5667. [PubMed] [Google Scholar]
  59. Lucas C. A., Czlonkowska A., Kreutzberg G. W. Regulation of acetylcholinesterase by nerve growth factor in the pheochromocytoma PC12 cell line. Neurosci Lett. 1980 Jul;18(3):333–337. doi: 10.1016/0304-3940(80)90307-9. [DOI] [PubMed] [Google Scholar]
  60. Lucas C. A., Edgar D., Thoenen H. Regulation of tyrosine hydroxylase and choline acetyltransferase activities by cell density in the PC12 rat pheochromocytoma clonal cell line. Exp Cell Res. 1979 Jun;121(1):79–86. doi: 10.1016/0014-4827(79)90446-4. [DOI] [PubMed] [Google Scholar]
  61. Machida C. M., Rodland K. D., Matrisian L., Magun B. E., Ciment G. NGF induction of the gene encoding the protease transin accompanies neuronal differentiation in PC12 cells. Neuron. 1989 Jun;2(6):1587–1596. doi: 10.1016/0896-6273(89)90047-0. [DOI] [PubMed] [Google Scholar]
  62. Machida C. M., Scott J. D., Ciment G. NGF-induction of the metalloproteinase-transin/stromelysin in PC12 cells: involvement of multiple protein kinases. J Cell Biol. 1991 Sep;114(5):1037–1048. doi: 10.1083/jcb.114.5.1037. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Maher P. A. Role of protein tyrosine phosphorylation in the NGF response. J Neurosci Res. 1989 Sep;24(1):29–37. doi: 10.1002/jnr.490240106. [DOI] [PubMed] [Google Scholar]
  64. Marini M., Zunica G., Bagnara G. P., Franceschi C. Effect of vanadate of PHA-induced proliferation of human lymphocytes from young and old subjects. Biochem Biophys Res Commun. 1987 Feb 13;142(3):836–842. doi: 10.1016/0006-291x(87)91489-6. [DOI] [PubMed] [Google Scholar]
  65. Matsushime H., Roussel M. F., Ashmun R. A., Sherr C. J. Colony-stimulating factor 1 regulates novel cyclins during the G1 phase of the cell cycle. Cell. 1991 May 17;65(4):701–713. doi: 10.1016/0092-8674(91)90101-4. [DOI] [PubMed] [Google Scholar]
  66. Miyasaka T., Sternberg D. W., Miyasaka J., Sherline P., Saltiel A. R. Nerve growth factor stimulates protein tyrosine phosphorylation in PC-12 pheochromocytoma cells. Proc Natl Acad Sci U S A. 1991 Apr 1;88(7):2653–2657. doi: 10.1073/pnas.88.7.2653. [DOI] [PMC free article] [PubMed] [Google Scholar]
  67. Mobley W. C., Schenker A., Shooter E. M. Characterization and isolation of proteolytically modified nerve growth factor. Biochemistry. 1976 Dec 14;15(25):5543–5552. doi: 10.1021/bi00670a019. [DOI] [PubMed] [Google Scholar]
  68. Nishibe S., Wahl M. I., Hernández-Sotomayor S. M., Tonks N. K., Rhee S. G., Carpenter G. Increase of the catalytic activity of phospholipase C-gamma 1 by tyrosine phosphorylation. Science. 1990 Nov 30;250(4985):1253–1256. doi: 10.1126/science.1700866. [DOI] [PubMed] [Google Scholar]
  69. Nurse P. Universal control mechanism regulating onset of M-phase. Nature. 1990 Apr 5;344(6266):503–508. doi: 10.1038/344503a0. [DOI] [PubMed] [Google Scholar]
  70. Obermeier A., Halfter H., Wiesmüller K. H., Jung G., Schlessinger J., Ullrich A. Tyrosine 785 is a major determinant of Trk--substrate interaction. EMBO J. 1993 Mar;12(3):933–941. doi: 10.1002/j.1460-2075.1993.tb05734.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  71. Pallen C. J., Tong P. H. Elevation of membrane tyrosine phosphatase activity in density-dependent growth-arrested fibroblasts. Proc Natl Acad Sci U S A. 1991 Aug 15;88(16):6996–7000. doi: 10.1073/pnas.88.16.6996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  72. Pessin M. S., Altin J. G., Jarpe M., Tansley F., Bradshaw R. A., Raben D. M. Carbachol stimulates a different phospholipid metabolism than nerve growth factor and basic fibroblast growth factor in PC12 cells. Cell Regul. 1991 May;2(5):383–390. doi: 10.1091/mbc.2.5.383. [DOI] [PMC free article] [PubMed] [Google Scholar]
  73. Piwnica-Worms H., Saunders K. B., Roberts T. M., Smith A. E., Cheng S. H. Tyrosine phosphorylation regulates the biochemical and biological properties of pp60c-src. Cell. 1987 Apr 10;49(1):75–82. doi: 10.1016/0092-8674(87)90757-4. [DOI] [PubMed] [Google Scholar]
  74. Preiss J., Loomis C. R., Bishop W. R., Stein R., Niedel J. E., Bell R. M. Quantitative measurement of sn-1,2-diacylglycerols present in platelets, hepatocytes, and ras- and sis-transformed normal rat kidney cells. J Biol Chem. 1986 Jul 5;261(19):8597–8600. [PubMed] [Google Scholar]
  75. Radeke M. J., Misko T. P., Hsu C., Herzenberg L. A., Shooter E. M. Gene transfer and molecular cloning of the rat nerve growth factor receptor. Nature. 1987 Feb 12;325(6105):593–597. doi: 10.1038/325593a0. [DOI] [PubMed] [Google Scholar]
  76. Raffioni S., Bradshaw R. A. Activation of phosphatidylinositol 3-kinase by epidermal growth factor, basic fibroblast growth factor, and nerve growth factor in PC12 pheochromocytoma cells. Proc Natl Acad Sci U S A. 1992 Oct 1;89(19):9121–9125. doi: 10.1073/pnas.89.19.9121. [DOI] [PMC free article] [PubMed] [Google Scholar]
  77. Ramanadham M., Kern M. Differential effect of vanadate on DNA synthesis induced by mitogens in T and B lymphocytes. Mol Cell Biochem. 1983;51(1):67–71. doi: 10.1007/BF00215587. [DOI] [PubMed] [Google Scholar]
  78. Rausch D. M., Dickens G., Doll S., Fujita K., Koizumi S., Rudkin B. B., Tocco M., Eiden L. E., Guroff G. Differentiation of PC12 cells with v-src: comparison with nerve growth factor. J Neurosci Res. 1989 Sep;24(1):49–58. doi: 10.1002/jnr.490240108. [DOI] [PubMed] [Google Scholar]
  79. Rhee S. G. Inositol phospholipids-specific phospholipase C: interaction of the gamma 1 isoform with tyrosine kinase. Trends Biochem Sci. 1991 Aug;16(8):297–301. doi: 10.1016/0968-0004(91)90122-c. [DOI] [PubMed] [Google Scholar]
  80. Rieger F., Shelanski M. L., Greene L. A. The effects of nerve growth factor on acetylcholinesterase and its multiple forms in cultures of rat PC12 pheochromocytoma cells: increased total specific activity and appearance of the 16 S molecular form. Dev Biol. 1980 Apr;76(1):238–243. doi: 10.1016/0012-1606(80)90376-0. [DOI] [PubMed] [Google Scholar]
  81. Role of vanadium in biology. Symposium summary. Fed Proc. 1986 Feb;45(2):123–132. [PubMed] [Google Scholar]
  82. Rydel R. E., Greene L. A. Acidic and basic fibroblast growth factors promote stable neurite outgrowth and neuronal differentiation in cultures of PC12 cells. J Neurosci. 1987 Nov;7(11):3639–3653. doi: 10.1523/JNEUROSCI.07-11-03639.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  83. Sato B., Miyashita Y., Maeda Y., Noma K., Kishimoto S., Matsumoto K. Effects of estrogen and vanadate on the proliferation of newly established transformed mouse Leydig cell line in vitro. Endocrinology. 1987 Mar;120(3):1112–1120. doi: 10.1210/endo-120-3-1112. [DOI] [PubMed] [Google Scholar]
  84. Satoh T., Nakamura S., Taga T., Matsuda T., Hirano T., Kishimoto T., Kaziro Y. Induction of neuronal differentiation in PC12 cells by B-cell stimulatory factor 2/interleukin 6. Mol Cell Biol. 1988 Aug;8(8):3546–3549. doi: 10.1128/mcb.8.8.3546. [DOI] [PMC free article] [PubMed] [Google Scholar]
  85. Savage C. R., Jr, Cohen S. Epidermal growth factor and a new derivative. Rapid isolation procedures and biological and chemical characterization. J Biol Chem. 1972 Dec 10;247(23):7609–7611. [PubMed] [Google Scholar]
  86. Schanen-King C., Nel A., Williams L. K., Landreth G. Nerve growth factor stimulates the tyrosine phosphorylation of MAP2 kinase in PC12 cells. Neuron. 1991 Jun;6(6):915–922. doi: 10.1016/0896-6273(91)90232-o. [DOI] [PubMed] [Google Scholar]
  87. Schubert D., Heinemann S., Kidokoro Y. Cholinergic metabolism and synapse formation by a rat nerve cell line. Proc Natl Acad Sci U S A. 1977 Jun;74(6):2579–2583. doi: 10.1073/pnas.74.6.2579. [DOI] [PMC free article] [PubMed] [Google Scholar]
  88. Seger R., Ahn N. G., Boulton T. G., Yancopoulos G. D., Panayotatos N., Radziejewska E., Ericsson L., Bratlien R. L., Cobb M. H., Krebs E. G. Microtubule-associated protein 2 kinases, ERK1 and ERK2, undergo autophosphorylation on both tyrosine and threonine residues: implications for their mechanism of activation. Proc Natl Acad Sci U S A. 1991 Jul 15;88(14):6142–6146. doi: 10.1073/pnas.88.14.6142. [DOI] [PMC free article] [PubMed] [Google Scholar]
  89. Sigmund O., Naor Z., Anderson D. J., Stein R. Effect of nerve growth factor and fibroblast growth factor on SCG10 and c-fos expression and neurite outgrowth in protein kinase C-depleted PC12 cells. J Biol Chem. 1990 Feb 5;265(4):2257–2261. [PubMed] [Google Scholar]
  90. Smith J. B. Vanadium ions stimulate DNA synthesis in Swiss mouse 3T3 and 3T6 cells. Proc Natl Acad Sci U S A. 1983 Oct;80(20):6162–6166. doi: 10.1073/pnas.80.20.6162. [DOI] [PMC free article] [PubMed] [Google Scholar]
  91. Stein R., Mori N., Matthews K., Lo L. C., Anderson D. J. The NGF-inducible SCG10 mRNA encodes a novel membrane-bound protein present in growth cones and abundant in developing neurons. Neuron. 1988 Aug;1(6):463–476. doi: 10.1016/0896-6273(88)90177-8. [DOI] [PubMed] [Google Scholar]
  92. Stein R., Orit S., Anderson D. J. The induction of a neural-specific gene, SCG10, by nerve growth factor in PC12 cells is transcriptional, protein synthesis dependent, and glucocorticoid inhibitable. Dev Biol. 1988 Jun;127(2):316–325. doi: 10.1016/0012-1606(88)90318-1. [DOI] [PubMed] [Google Scholar]
  93. Strausfeld U., Labbé J. C., Fesquet D., Cavadore J. C., Picard A., Sadhu K., Russell P., Dorée M. Dephosphorylation and activation of a p34cdc2/cyclin B complex in vitro by human CDC25 protein. Nature. 1991 May 16;351(6323):242–245. doi: 10.1038/351242a0. [DOI] [PubMed] [Google Scholar]
  94. Streuli M., Krueger N. X., Thai T., Tang M., Saito H. Distinct functional roles of the two intracellular phosphatase like domains of the receptor-linked protein tyrosine phosphatases LCA and LAR. EMBO J. 1990 Aug;9(8):2399–2407. doi: 10.1002/j.1460-2075.1990.tb07415.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  95. Szász I., Sarkadi B., Enyedi A., Gárdos G. Ca-transport and CaMg-ATPase activity in human red cell preparations. Acta Biol Med Ger. 1981;40(4-5):429–436. [PubMed] [Google Scholar]
  96. Tojo A., Kasuga M., Urabe A., Takaku F. Vanadate can replace interleukin 3 for transient growth of factor-dependent cells. Exp Cell Res. 1987 Jul;171(1):16–23. doi: 10.1016/0014-4827(87)90247-3. [DOI] [PubMed] [Google Scholar]
  97. Tonks N. K., Diltz C. D., Fischer E. H. Characterization of the major protein-tyrosine-phosphatases of human placenta. J Biol Chem. 1988 May 15;263(14):6731–6737. [PubMed] [Google Scholar]
  98. Tsao H., Aletta J. M., Greene L. A. Nerve growth factor and fibroblast growth factor selectively activate a protein kinase that phosphorylates high molecular weight microtubule-associated proteins. Detection, partial purification, and characterization in PC12 cells. J Biol Chem. 1990 Sep 15;265(26):15471–15480. [PubMed] [Google Scholar]
  99. Tsao H., Greene L. A. The roles of macromolecular synthesis and phosphorylation in the regulation of a protein kinase activity transiently stimulated by nerve growth factor. J Biol Chem. 1991 Jul 15;266(20):12981–12988. [PubMed] [Google Scholar]
  100. Vetter M. L., Martin-Zanca D., Parada L. F., Bishop J. M., Kaplan D. R. Nerve growth factor rapidly stimulates tyrosine phosphorylation of phospholipase C-gamma 1 by a kinase activity associated with the product of the trk protooncogene. Proc Natl Acad Sci U S A. 1991 Jul 1;88(13):5650–5654. doi: 10.1073/pnas.88.13.5650. [DOI] [PMC free article] [PubMed] [Google Scholar]
  101. Vila J., Weber M. J. Mitogen-stimulated tyrosine phosphorylation of a 42-kD cellular protein: evidence for a protein kinase-C requirement. J Cell Physiol. 1988 May;135(2):285–292. doi: 10.1002/jcp.1041350216. [DOI] [PubMed] [Google Scholar]
  102. Wagner J. A. The fibroblast growth factors: an emerging family of neural growth factors. Curr Top Microbiol Immunol. 1991;165:95–118. doi: 10.1007/978-3-642-75747-1_6. [DOI] [PubMed] [Google Scholar]
  103. Werdan K., Bauriedel G., Bozsik M., Krawietz W., Erdmann E. Effects of vanadate in cultured rat heart muscle cells. Vanadate transport, intracellular binding and vanadate-induced changes in beating and in active cation flux. Biochim Biophys Acta. 1980 Apr 10;597(2):364–383. doi: 10.1016/0005-2736(80)90113-3. [DOI] [PubMed] [Google Scholar]
  104. Wright T. M., Rangan L. A., Shin H. S., Raben D. M. Kinetic analysis of 1,2-diacylglycerol mass levels in cultured fibroblasts. Comparison of stimulation by alpha-thrombin and epidermal growth factor. J Biol Chem. 1988 Jul 5;263(19):9374–9380. [PubMed] [Google Scholar]
  105. Zheng X. M., Wang Y., Pallen C. J. Cell transformation and activation of pp60c-src by overexpression of a protein tyrosine phosphatase. Nature. 1992 Sep 24;359(6393):336–339. doi: 10.1038/359336a0. [DOI] [PubMed] [Google Scholar]

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