Skip to main content
PMC home page
The Journal of Cell Biology logoLink to The Journal of Cell Biology
. 1996 Jan 1;132(1):91–99. doi: 10.1083/jcb.132.1.91

Involvement of Fyn tyrosine kinase in progression of cytokinesis of B lymphocyte progenitor

PMCID: PMC2120696  PMID: 8567733

Abstract

We analyzed the role of Fyn tyrosine kinase in cell cycle progression of B lymphocyte progenitor (pro B cell). Whereas there were no substantial defects in the intramarrow B cell genesis in the fyn(-) mouse, and long-term proliferation of fyn(-) pro B cells was maintained in vitro under a serum containing culture condition, the cell cycle was arrested at G2/M upon serum deprivation. Morphological analyses demonstrated that the cytokinesis of fyn(-) pro B cells was retarded in the presence of serum and that the entry of fyn(-) pro B cells into late telophase was completely blocked under the serum-free condition. In contrast, the earlier phases of mitosis of fyn(-) pro B cells proceeded normally without FCS. This failure to initiate late telophase resulted in the accumulation of elliptical binucleated cells that might be the outcome of the nuclear division without cytokinesis. Consistent with this defect in the progression of cytokinesis, Fyn was localized in the midspace of dividing pro B cells at anaphase. These results suggested that Fyn localizes at the midspace of dividing pro B cells and regulates the progression of cytokinesis.

Full Text

The Full Text of this article is available as a PDF (2.0 MB).

Selected References

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

  1. Appleby M. W., Gross J. A., Cooke M. P., Levin S. D., Qian X., Perlmutter R. M. Defective T cell receptor signaling in mice lacking the thymic isoform of p59fyn. Cell. 1992 Sep 4;70(5):751–763. doi: 10.1016/0092-8674(92)90309-z. [DOI] [PubMed] [Google Scholar]
  2. Bare D. J., Lauder J. M., Wilkie M. B., Maness P. F. p59fyn in rat brain is localized in developing axonal tracts and subpopulations of adult neurons and glia. Oncogene. 1993 Jun;8(6):1429–1436. [PubMed] [Google Scholar]
  3. Beggs H. E., Soriano P., Maness P. F. NCAM-dependent neurite outgrowth is inhibited in neurons from Fyn-minus mice. J Cell Biol. 1994 Nov;127(3):825–833. doi: 10.1083/jcb.127.3.825. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Brinkley B. R., Fistel S. H., Marcum J. M., Pardue R. L. Microtubules in cultured cells; indirect immunofluorescent staining with tubulin antibody. Int Rev Cytol. 1980;63:59–95. doi: 10.1016/s0074-7696(08)61757-x. [DOI] [PubMed] [Google Scholar]
  5. Brizuela L., Ulug E. T., Jones M. A., Courtneidge S. A. Induction of interleukin-2 transcription by the hamster polyomavirus middle T antigen: a role for Fyn in T cell signal transduction. Eur J Immunol. 1995 Feb;25(2):385–393. doi: 10.1002/eji.1830250212. [DOI] [PubMed] [Google Scholar]
  6. Burkhardt A. L., Brunswick M., Bolen J. B., Mond J. J. Anti-immunoglobulin stimulation of B lymphocytes activates src-related protein-tyrosine kinases. Proc Natl Acad Sci U S A. 1991 Aug 15;88(16):7410–7414. doi: 10.1073/pnas.88.16.7410. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cooke M. P., Abraham K. M., Forbush K. A., Perlmutter R. M. Regulation of T cell receptor signaling by a src family protein-tyrosine kinase (p59fyn). Cell. 1991 Apr 19;65(2):281–291. doi: 10.1016/0092-8674(91)90162-r. [DOI] [PubMed] [Google Scholar]
  8. Cool D. E., Andreassen P. R., Tonks N. K., Krebs E. G., Fischer E. H., Margolis R. L. Cytokinetic failure and asynchronous nuclear division in BHK cells overexpressing a truncated protein-tyrosine-phosphatase. Proc Natl Acad Sci U S A. 1992 Jun 15;89(12):5422–5426. doi: 10.1073/pnas.89.12.5422. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Erpel T., Courtneidge S. A. Src family protein tyrosine kinases and cellular signal transduction pathways. Curr Opin Cell Biol. 1995 Apr;7(2):176–182. doi: 10.1016/0955-0674(95)80025-5. [DOI] [PubMed] [Google Scholar]
  10. Fukami Y., Nakamura T., Nakayama A., Kanehisa T. Phosphorylation of tyrosine residues of calmodulin in Rous sarcoma virus-transformed cells. Proc Natl Acad Sci U S A. 1986 Jun;83(12):4190–4193. doi: 10.1073/pnas.83.12.4190. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Fukasawa K., Vande Woude G. F. Mos overexpression in Swiss 3T3 cells induces meiotic-like alterations of the mitotic spindle. Proc Natl Acad Sci U S A. 1995 Apr 11;92(8):3430–3434. doi: 10.1073/pnas.92.8.3430. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Fumagalli S., Totty N. F., Hsuan J. J., Courtneidge S. A. A target for Src in mitosis. Nature. 1994 Apr 28;368(6474):871–874. doi: 10.1038/368871a0. [DOI] [PubMed] [Google Scholar]
  13. Fusaki N., Semba K., Katagiri T., Suzuki G., Matsuda S., Yamamoto T. Characterization of p59fyn-mediated signal transduction on T cell activation. Int Immunol. 1994 Aug;6(8):1245–1255. doi: 10.1093/intimm/6.8.1245. [DOI] [PubMed] [Google Scholar]
  14. Grabstein K. H., Waldschmidt T. J., Finkelman F. D., Hess B. W., Alpert A. R., Boiani N. E., Namen A. E., Morrissey P. J. Inhibition of murine B and T lymphopoiesis in vivo by an anti-interleukin 7 monoclonal antibody. J Exp Med. 1993 Jul 1;178(1):257–264. doi: 10.1084/jem.178.1.257. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Grant S. G., O'Dell T. J., Karl K. A., Stein P. L., Soriano P., Kandel E. R. Impaired long-term potentiation, spatial learning, and hippocampal development in fyn mutant mice. Science. 1992 Dec 18;258(5090):1903–1910. doi: 10.1126/science.1361685. [DOI] [PubMed] [Google Scholar]
  16. Hayashi S., Kunisada T., Ogawa M., Sudo T., Kodama H., Suda T., Nishikawa S., Nishikawa S. Stepwise progression of B lineage differentiation supported by interleukin 7 and other stromal cell molecules. J Exp Med. 1990 May 1;171(5):1683–1695. doi: 10.1084/jem.171.5.1683. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Katagiri K., Katagiri T., Kajiyama K., Yamamoto T., Yoshida T. Tyrosine-phosphorylation of tubulin during monocytic differentiation of HL-60 cells. J Immunol. 1993 Jan 15;150(2):585–593. [PubMed] [Google Scholar]
  18. Kobayashi N., Kono T., Hatakeyama M., Minami Y., Miyazaki T., Perlmutter R. M., Taniguchi T. Functional coupling of the src-family protein tyrosine kinases p59fyn and p53/56lyn with the interleukin 2 receptor: implications for redundancy and pleiotropism in cytokine signal transduction. Proc Natl Acad Sci U S A. 1993 May 1;90(9):4201–4205. doi: 10.1073/pnas.90.9.4201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Krishan A. Cytochalasin-B: time-lapse cinematographic studies on its effects on cytokinesis. J Cell Biol. 1972 Sep;54(3):657–664. doi: 10.1083/jcb.54.3.657. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Ley S. C., Marsh M., Bebbington C. R., Proudfoot K., Jordan P. Distinct intracellular localization of Lck and Fyn protein tyrosine kinases in human T lymphocytes. J Cell Biol. 1994 May;125(3):639–649. doi: 10.1083/jcb.125.3.639. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Ley S. C., Verbi W., Pappin D. J., Druker B., Davies A. A., Crumpton M. J. Tyrosine phosphorylation of alpha tubulin in human T lymphocytes. Eur J Immunol. 1994 Jan;24(1):99–106. doi: 10.1002/eji.1830240116. [DOI] [PubMed] [Google Scholar]
  22. Margolis R. L., Andreassen P. R. The telophase disc: its possible role in mammalian cell cleavage. Bioessays. 1993 Mar;15(3):201–207. doi: 10.1002/bies.950150310. [DOI] [PubMed] [Google Scholar]
  23. Matten W. T., Aubry M., West J., Maness P. F. Tubulin is phosphorylated at tyrosine by pp60c-src in nerve growth cone membranes. J Cell Biol. 1990 Nov;111(5 Pt 1):1959–1970. doi: 10.1083/jcb.111.5.1959. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Perlmutter R. M., Levin S. D., Appleby M. W., Anderson S. J., Alberola-Ila J. Regulation of lymphocyte function by protein phosphorylation. Annu Rev Immunol. 1993;11:451–499. doi: 10.1146/annurev.iy.11.040193.002315. [DOI] [PubMed] [Google Scholar]
  25. Peschon J. J., Morrissey P. J., Grabstein K. H., Ramsdell F. J., Maraskovsky E., Gliniak B. C., Park L. S., Ziegler S. F., Williams D. E., Ware C. B. Early lymphocyte expansion is severely impaired in interleukin 7 receptor-deficient mice. J Exp Med. 1994 Nov 1;180(5):1955–1960. doi: 10.1084/jem.180.5.1955. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Richard S., Yu D., Blumer K. J., Hausladen D., Olszowy M. W., Connelly P. A., Shaw A. S. Association of p62, a multifunctional SH2- and SH3-domain-binding protein, with src family tyrosine kinases, Grb2, and phospholipase C gamma-1. Mol Cell Biol. 1995 Jan;15(1):186–197. doi: 10.1128/mcb.15.1.186. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Rubin E. J., Gill D. M., Boquet P., Popoff M. R. Functional modification of a 21-kilodalton G protein when ADP-ribosylated by exoenzyme C3 of Clostridium botulinum. Mol Cell Biol. 1988 Jan;8(1):418–426. doi: 10.1128/mcb.8.1.418. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Samelson L. E., Phillips A. F., Luong E. T., Klausner R. D. Association of the fyn protein-tyrosine kinase with the T-cell antigen receptor. Proc Natl Acad Sci U S A. 1990 Jun;87(11):4358–4362. doi: 10.1073/pnas.87.11.4358. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Sanger J. W., Holtzer H. Cytochalasin-B: effects on cytokinesis, glycogen and 3 H-D-gluconse incorporation. Am J Anat. 1972 Oct;135(2):293–298. doi: 10.1002/aja.1001350214. [DOI] [PubMed] [Google Scholar]
  30. Seckinger P., Fougereau M. Activation of src family kinases in human pre-B cells by IL-7. J Immunol. 1994 Jul 1;153(1):97–109. [PubMed] [Google Scholar]
  31. Semba K., Nishizawa M., Miyajima N., Yoshida M. C., Sukegawa J., Yamanashi Y., Sasaki M., Yamamoto T., Toyoshima K. yes-related protooncogene, syn, belongs to the protein-tyrosine kinase family. Proc Natl Acad Sci U S A. 1986 Aug;83(15):5459–5463. doi: 10.1073/pnas.83.15.5459. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Shenoy S., Chackalaparampil I., Bagrodia S., Lin P. H., Shalloway D. Role of p34cdc2-mediated phosphorylations in two-step activation of pp60c-src during mitosis. Proc Natl Acad Sci U S A. 1992 Aug 1;89(15):7237–7241. doi: 10.1073/pnas.89.15.7237. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Shinkai Y., Rathbun G., Lam K. P., Oltz E. M., Stewart V., Mendelsohn M., Charron J., Datta M., Young F., Stall A. M. RAG-2-deficient mice lack mature lymphocytes owing to inability to initiate V(D)J rearrangement. Cell. 1992 Mar 6;68(5):855–867. doi: 10.1016/0092-8674(92)90029-c. [DOI] [PubMed] [Google Scholar]
  34. Stein P. L., Lee H. M., Rich S., Soriano P. pp59fyn mutant mice display differential signaling in thymocytes and peripheral T cells. Cell. 1992 Sep 4;70(5):741–750. doi: 10.1016/0092-8674(92)90308-y. [DOI] [PubMed] [Google Scholar]
  35. Sudo T., Nishikawa S., Ohno N., Akiyama N., Tamakoshi M., Yoshida H., Nishikawa S. Expression and function of the interleukin 7 receptor in murine lymphocytes. Proc Natl Acad Sci U S A. 1993 Oct 1;90(19):9125–9129. doi: 10.1073/pnas.90.19.9125. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Takeuchi M., Kuramochi S., Fusaki N., Nada S., Kawamura-Tsuzuku J., Matsuda S., Semba K., Toyoshima K., Okada M., Yamamoto T. Functional and physical interaction of protein-tyrosine kinases Fyn and Csk in the T-cell signaling system. J Biol Chem. 1993 Dec 25;268(36):27413–27419. [PubMed] [Google Scholar]
  37. Taylor S. J., Shalloway D. The cell cycle and c-Src. Curr Opin Genet Dev. 1993 Feb;3(1):26–34. doi: 10.1016/s0959-437x(05)80337-5. [DOI] [PubMed] [Google Scholar]
  38. Umemori H., Sato S., Yagi T., Aizawa S., Yamamoto T. Initial events of myelination involve Fyn tyrosine kinase signalling. Nature. 1994 Feb 10;367(6463):572–576. doi: 10.1038/367572a0. [DOI] [PubMed] [Google Scholar]
  39. Venkitaraman A. R., Cowling R. J. Interleukin 7 receptor functions by recruiting the tyrosine kinase p59fyn through a segment of its cytoplasmic tail. Proc Natl Acad Sci U S A. 1992 Dec 15;89(24):12083–12087. doi: 10.1073/pnas.89.24.12083. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Welsh M. J., Dedman J. R., Brinkley B. R., Means A. R. Tubulin and calmodulin. Effects of microtubule and microfilament inhibitors on localization in the mitotic apparatus. J Cell Biol. 1979 Jun;81(3):624–634. doi: 10.1083/jcb.81.3.624. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Yagi T., Aizawa S., Tokunaga T., Shigetani Y., Takeda N., Ikawa Y. A role for Fyn tyrosine kinase in the suckling behaviour of neonatal mice. Nature. 1993 Dec 23;366(6457):742–745. doi: 10.1038/366742a0. [DOI] [PubMed] [Google Scholar]
  42. Yasunaga M., Wang F., Kunisada T., Nishikawa S., Nishikawa S. Cell cycle control of c-kit+IL-7R+ B precursor cells by two distinct signals derived from IL-7 receptor and c-kit in a fully defined medium. J Exp Med. 1995 Aug 1;182(2):315–323. doi: 10.1084/jem.182.2.315. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The Journal of Cell Biology are provided here courtesy of The Rockefeller University Press

RESOURCES