Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1994 Mar 1;91(5):1819–1823. doi: 10.1073/pnas.91.5.1819

Multiple tyrosine protein kinases in rat hippocampal neurons: isolation of Ptk-3, a receptor expressed in proliferative zones of the developing brain.

M P Sánchez 1, P Tapley 1, S S Saini 1, B He 1, D Pulido 1, M Barbacid 1
PMCID: PMC43255  PMID: 8127887

Abstract

Tyrosine protein kinases are likely to play an important role in the maintenance and/or development of the nervous system. In this study we have used the PCR cloning technique to isolate sequences derived from tyrosine kinase genes expressed in cultured hippocampal neurons obtained from 17.5-day-old rat embryos. Nucleotide sequence analysis of 209 independent clones revealed sequences derived from 25 tyrosine kinases, of which two corresponded to previously unreported genes. One of the PCR clones, ptk-2, belongs to the Jak family of cytoplasmic tyrosine kinases. The second clone, ptk-3, was derived from a gene encoding an additional class of tyrosine kinase receptors whose extracellular domains contain regions of homology with coagulation factors V and VIII and complement component C1. Transcripts encoding the Ptk-3 receptor are present in a variety of embryonic and adult tissues with highest levels observed in brain. During development, ptk-3 transcripts are most abundant in the proliferative neuroepithelial cells of the ventricular zone, raising the possibility that this receptor may play an important role in the generation of the mammalian nervous system.

Full text

PDF
1819

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Barbacid M., Lamballe F., Pulido D., Klein R. The trk family of tyrosine protein kinase receptors. Biochim Biophys Acta. 1991 Dec 10;1072(2-3):115–127. doi: 10.1016/0304-419x(91)90010-i. [DOI] [PubMed] [Google Scholar]
  2. Barbacid M. Nerve growth factor: a tale of two receptors. Oncogene. 1993 Aug;8(8):2033–2042. [PubMed] [Google Scholar]
  3. Barde Y. A. Trophic factors and neuronal survival. Neuron. 1989 Jun;2(6):1525–1534. doi: 10.1016/0896-6273(89)90040-8. [DOI] [PubMed] [Google Scholar]
  4. Bustelo X. R., Rubin S. D., Suen K. L., Carrasco D., Barbacid M. Developmental expression of the vav protooncogene. Cell Growth Differ. 1993 Apr;4(4):297–308. [PubMed] [Google Scholar]
  5. Chan J., Watt V. M. eek and erk, new members of the eph subclass of receptor protein-tyrosine kinases. Oncogene. 1991 Jun;6(6):1057–1061. [PubMed] [Google Scholar]
  6. Falls D. L., Rosen K. M., Corfas G., Lane W. S., Fischbach G. D. ARIA, a protein that stimulates acetylcholine receptor synthesis, is a member of the neu ligand family. Cell. 1993 Mar 12;72(5):801–815. doi: 10.1016/0092-8674(93)90407-h. [DOI] [PubMed] [Google Scholar]
  7. Fantl W. J., Johnson D. E., Williams L. T. Signalling by receptor tyrosine kinases. Annu Rev Biochem. 1993;62:453–481. doi: 10.1146/annurev.bi.62.070193.002321. [DOI] [PubMed] [Google Scholar]
  8. Gilardi-Hebenstreit P., Nieto M. A., Frain M., Mattéi M. G., Chestier A., Wilkinson D. G., Charnay P. An Eph-related receptor protein tyrosine kinase gene segmentally expressed in the developing mouse hindbrain. Oncogene. 1992 Dec;7(12):2499–2506. [PubMed] [Google Scholar]
  9. Harpur A. G., Andres A. C., Ziemiecki A., Aston R. R., Wilks A. F. JAK2, a third member of the JAK family of protein tyrosine kinases. Oncogene. 1992 Jul;7(7):1347–1353. [PubMed] [Google Scholar]
  10. Jennings C. G., Dyer S. M., Burden S. J. Muscle-specific trk-related receptor with a kringle domain defines a distinct class of receptor tyrosine kinases. Proc Natl Acad Sci U S A. 1993 Apr 1;90(7):2895–2899. doi: 10.1073/pnas.90.7.2895. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Jing S., Tapley P., Barbacid M. Nerve growth factor mediates signal transduction through trk homodimer receptors. Neuron. 1992 Dec;9(6):1067–1079. doi: 10.1016/0896-6273(92)90066-m. [DOI] [PubMed] [Google Scholar]
  12. Johnson J. D., Edman J. C., Rutter W. J. A receptor tyrosine kinase found in breast carcinoma cells has an extracellular discoidin I-like domain. Proc Natl Acad Sci U S A. 1993 Jun 15;90(12):5677–5681. doi: 10.1073/pnas.90.12.5677. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kane W. H., Davie E. W. Cloning of a cDNA coding for human factor V, a blood coagulation factor homologous to factor VIII and ceruloplasmin. Proc Natl Acad Sci U S A. 1986 Sep;83(18):6800–6804. doi: 10.1073/pnas.83.18.6800. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. 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]
  15. Kelman Z., Simon-Chazottes D., Guénet J. L., Yarden Y. The murine vik gene (chromosome 9) encodes a putative receptor with unique protein kinase motifs. Oncogene. 1993 Jan;8(1):37–44. [PubMed] [Google Scholar]
  16. Klein R., Conway D., Parada L. F., Barbacid M. The trkB tyrosine protein kinase gene codes for a second neurogenic receptor that lacks the catalytic kinase domain. Cell. 1990 May 18;61(4):647–656. doi: 10.1016/0092-8674(90)90476-u. [DOI] [PubMed] [Google Scholar]
  17. 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]
  18. Klein R., Smeyne R. J., Wurst W., Long L. K., Auerbach B. A., Joyner A. L., Barbacid M. Targeted disruption of the trkB neurotrophin receptor gene results in nervous system lesions and neonatal death. Cell. 1993 Oct 8;75(1):113–122. [PubMed] [Google Scholar]
  19. Lai C., Lemke G. An extended family of protein-tyrosine kinase genes differentially expressed in the vertebrate nervous system. Neuron. 1991 May;6(5):691–704. doi: 10.1016/0896-6273(91)90167-x. [DOI] [PubMed] [Google Scholar]
  20. Larocca D., Peterson J. A., Urrea R., Kuniyoshi J., Bistrain A. M., Ceriani R. L. A Mr 46,000 human milk fat globule protein that is highly expressed in human breast tumors contains factor VIII-like domains. Cancer Res. 1991 Sep 15;51(18):4994–4998. [PubMed] [Google Scholar]
  21. Lindberg R. A., Hunter T. cDNA cloning and characterization of eck, an epithelial cell receptor protein-tyrosine kinase in the eph/elk family of protein kinases. Mol Cell Biol. 1990 Dec;10(12):6316–6324. doi: 10.1128/mcb.10.12.6316. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Maness P. F., Cox M. E. Protein tyrosine kinases in nervous system development. Semin Cell Biol. 1992 Apr;3(2):117–126. doi: 10.1016/s1043-4682(10)80021-2. [DOI] [PubMed] [Google Scholar]
  23. Masiakowski P., Carroll R. D. A novel family of cell surface receptors with tyrosine kinase-like domain. J Biol Chem. 1992 Dec 25;267(36):26181–26190. [PubMed] [Google Scholar]
  24. 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]
  25. Poole S., Firtel R. A., Lamar E., Rowekamp W. Sequence and expression of the discoidin I gene family in Dictyostelium discoideum. J Mol Biol. 1981 Dec 5;153(2):273–289. doi: 10.1016/0022-2836(81)90278-3. [DOI] [PubMed] [Google Scholar]
  26. Schlessinger J., Ullrich A. Growth factor signaling by receptor tyrosine kinases. Neuron. 1992 Sep;9(3):383–391. doi: 10.1016/0896-6273(92)90177-f. [DOI] [PubMed] [Google Scholar]
  27. Scholz W. K., Palfrey H. C. Glutamate-stimulated protein phosphorylation in cultured hippocampal pyramidal neurons. J Neurosci. 1991 Aug;11(8):2422–2432. doi: 10.1523/JNEUROSCI.11-08-02422.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Stubbs J. D., Lekutis C., Singer K. L., Bui A., Yuzuki D., Srinivasan U., Parry G. cDNA cloning of a mouse mammary epithelial cell surface protein reveals the existence of epidermal growth factor-like domains linked to factor VIII-like sequences. Proc Natl Acad Sci U S A. 1990 Nov;87(21):8417–8421. doi: 10.1073/pnas.87.21.8417. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Takagi S., Hirata T., Agata K., Mochii M., Eguchi G., Fujisawa H. The A5 antigen, a candidate for the neuronal recognition molecule, has homologies to complement components and coagulation factors. Neuron. 1991 Aug;7(2):295–307. doi: 10.1016/0896-6273(91)90268-5. [DOI] [PubMed] [Google Scholar]
  30. Tosi M., Duponchel C., Meo T., Julier C. Complete cDNA sequence of human complement Cls and close physical linkage of the homologous genes Cls and Clr. Biochemistry. 1987 Dec 29;26(26):8516–8524. doi: 10.1021/bi00400a004. [DOI] [PubMed] [Google Scholar]
  31. Ullrich A., Bell J. R., Chen E. Y., Herrera R., Petruzzelli L. M., Dull T. J., Gray A., Coussens L., Liao Y. C., Tsubokawa M. Human insulin receptor and its relationship to the tyrosine kinase family of oncogenes. 1985 Feb 28-Mar 6Nature. 313(6005):756–761. doi: 10.1038/313756a0. [DOI] [PubMed] [Google Scholar]
  32. Velazquez L., Fellous M., Stark G. R., Pellegrini S. A protein tyrosine kinase in the interferon alpha/beta signaling pathway. Cell. 1992 Jul 24;70(2):313–322. doi: 10.1016/0092-8674(92)90105-l. [DOI] [PubMed] [Google Scholar]
  33. Walicke P. A. Novel neurotrophic factors, receptors, and oncogenes. Annu Rev Neurosci. 1989;12:103–126. doi: 10.1146/annurev.ne.12.030189.000535. [DOI] [PubMed] [Google Scholar]
  34. Wilks A. F., Harpur A. G., Kurban R. R., Ralph S. J., Zürcher G., Ziemiecki A. Two novel protein-tyrosine kinases, each with a second phosphotransferase-related catalytic domain, define a new class of protein kinase. Mol Cell Biol. 1991 Apr;11(4):2057–2065. doi: 10.1128/mcb.11.4.2057. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Witthuhn B. A., Quelle F. W., Silvennoinen O., Yi T., Tang B., Miura O., Ihle J. N. JAK2 associates with the erythropoietin receptor and is tyrosine phosphorylated and activated following stimulation with erythropoietin. Cell. 1993 Jul 30;74(2):227–236. doi: 10.1016/0092-8674(93)90414-l. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES