Abstract
A gene encoding a unique protein-tyrosine kinase was isolated by PCR from undifferentiated embryonic stem (ES) cells. The gene, Emsk (embryonic stem cell kinase), is expressed in a number of different lymphoid and myeloid hematopoietic lineages and has been shown to be identical to the recently isolated focal adhesion-associated kinase gene (Fadk). Within the nonlymphoid lineages analyzed, Emsk/Fadk was found to be expressed in primitive and definitive erythroid cells but not in mast cells or macrophages. All CD5+ (B-1a) B cells tested, as well as freshly isolated conventional (B-2) B cells, expressed readily detectable levels of Emsk/Fadk. Within the T-cell lineage, Emsk/Fadk was expressed in V gamma 5 gamma/delta cells as well as in immature alpha/beta cells found within the thymus. As the alpha/beta T-cell population matures and exits the thymus, expression of Emsk/Fadk appears to be down regulated. The expression pattern outlined here suggests a role for Emsk/Fadk in multiple stages of hematopoietic development and raises the possibility that the kinase encoded by this gene has a broader spectrum of activities than was initially suggested.
Full text
PDF




Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Brotherton T. W., Chui D. H., Gauldie J., Patterson M. Hemoglobin ontogeny during normal mouse fetal development. Proc Natl Acad Sci U S A. 1979 Jun;76(6):2853–2857. doi: 10.1073/pnas.76.6.2853. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Burridge K., Turner C. E., Romer L. H. Tyrosine phosphorylation of paxillin and pp125FAK accompanies cell adhesion to extracellular matrix: a role in cytoskeletal assembly. J Cell Biol. 1992 Nov;119(4):893–903. doi: 10.1083/jcb.119.4.893. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chabot B., Stephenson D. A., Chapman V. M., Besmer P., Bernstein A. The proto-oncogene c-kit encoding a transmembrane tyrosine kinase receptor maps to the mouse W locus. Nature. 1988 Sep 1;335(6185):88–89. doi: 10.1038/335088a0. [DOI] [PubMed] [Google Scholar]
- Chelly J., Kaplan J. C., Maire P., Gautron S., Kahn A. Transcription of the dystrophin gene in human muscle and non-muscle tissue. Nature. 1988 Jun 30;333(6176):858–860. doi: 10.1038/333858a0. [DOI] [PubMed] [Google Scholar]
- 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]
- Davidson W. F., Fredrickson T. N., Rudikoff E. K., Coffman R. L., Hartley J. W., Morse H. C., 3rd A unique series of lymphomas related to the Ly-1+ lineage of B lymphocyte differentiation. J Immunol. 1984 Aug;133(2):744–753. [PubMed] [Google Scholar]
- Geissler E. N., Ryan M. A., Housman D. E. The dominant-white spotting (W) locus of the mouse encodes the c-kit proto-oncogene. Cell. 1988 Oct 7;55(1):185–192. doi: 10.1016/0092-8674(88)90020-7. [DOI] [PubMed] [Google Scholar]
- Gould S. J., Subramani S., Scheffler I. E. Use of the DNA polymerase chain reaction for homology probing: isolation of partial cDNA or genomic clones encoding the iron-sulfur protein of succinate dehydrogenase from several species. Proc Natl Acad Sci U S A. 1989 Mar;86(6):1934–1938. doi: 10.1073/pnas.86.6.1934. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Guan J. L., Shalloway D. Regulation of focal adhesion-associated protein tyrosine kinase by both cellular adhesion and oncogenic transformation. Nature. 1992 Aug 20;358(6388):690–692. doi: 10.1038/358690a0. [DOI] [PubMed] [Google Scholar]
- Hanks S. K., Calalb M. B., Harper M. C., Patel S. K. Focal adhesion protein-tyrosine kinase phosphorylated in response to cell attachment to fibronectin. Proc Natl Acad Sci U S A. 1992 Sep 15;89(18):8487–8491. doi: 10.1073/pnas.89.18.8487. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hardy R. R., Hayakawa K. A developmental switch in B lymphopoiesis. Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11550–11554. doi: 10.1073/pnas.88.24.11550. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Havran W. L., Allison J. P. Developmentally ordered appearance of thymocytes expressing different T-cell antigen receptors. Nature. 1988 Sep 29;335(6189):443–445. doi: 10.1038/335443a0. [DOI] [PubMed] [Google Scholar]
- Havran W. L., Allison J. P. Origin of Thy-1+ dendritic epidermal cells of adult mice from fetal thymic precursors. Nature. 1990 Mar 1;344(6261):68–70. doi: 10.1038/344068a0. [DOI] [PubMed] [Google Scholar]
- Hayakawa K., Hardy R. R., Stall A. M., Herzenberg L. A., Herzenberg L. A. Immunoglobulin-bearing B cells reconstitute and maintain the murine Ly-1 B cell lineage. Eur J Immunol. 1986 Oct;16(10):1313–1316. doi: 10.1002/eji.1830161021. [DOI] [PubMed] [Google Scholar]
- Hunter T. Protein kinase classification. Methods Enzymol. 1991;200:3–37. doi: 10.1016/0076-6879(91)00125-g. [DOI] [PubMed] [Google Scholar]
- Hynes R. O. Integrins: versatility, modulation, and signaling in cell adhesion. Cell. 1992 Apr 3;69(1):11–25. doi: 10.1016/0092-8674(92)90115-s. [DOI] [PubMed] [Google Scholar]
- Ikuta K., Kina T., MacNeil I., Uchida N., Peault B., Chien Y. H., Weissman I. L. A developmental switch in thymic lymphocyte maturation potential occurs at the level of hematopoietic stem cells. Cell. 1990 Sep 7;62(5):863–874. doi: 10.1016/0092-8674(90)90262-d. [DOI] [PubMed] [Google Scholar]
- Kantor A. A new nomenclature for B cells. Immunol Today. 1991 Nov;12(11):388–388. doi: 10.1016/0167-5699(91)90135-G. [DOI] [PubMed] [Google Scholar]
- Keller G., Kennedy M., Papayannopoulou T., Wiles M. V. Hematopoietic commitment during embryonic stem cell differentiation in culture. Mol Cell Biol. 1993 Jan;13(1):473–486. doi: 10.1128/mcb.13.1.473. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kennedy M., Beug H., Wagner E. F., Keller G. Factor-dependent erythroid cell lines derived from mice transplanted with hematopoietic cells expressing the v-src oncogene. Blood. 1992 Jan 1;79(1):180–190. [PubMed] [Google Scholar]
- Kipps T. J. The CD5 B cell. Adv Immunol. 1989;47:117–185. doi: 10.1016/s0065-2776(08)60663-x. [DOI] [PubMed] [Google Scholar]
- Kornberg L., Earp H. S., Parsons J. T., Schaller M., Juliano R. L. Cell adhesion or integrin clustering increases phosphorylation of a focal adhesion-associated tyrosine kinase. J Biol Chem. 1992 Nov 25;267(33):23439–23442. [PubMed] [Google Scholar]
- Lee C. C., Wu X. W., Gibbs R. A., Cook R. G., Muzny D. M., Caskey C. T. Generation of cDNA probes directed by amino acid sequence: cloning of urate oxidase. Science. 1988 Mar 11;239(4845):1288–1291. doi: 10.1126/science.3344434. [DOI] [PubMed] [Google Scholar]
- Lipfert L., Haimovich B., Schaller M. D., Cobb B. S., Parsons J. T., Brugge J. S. Integrin-dependent phosphorylation and activation of the protein tyrosine kinase pp125FAK in platelets. J Cell Biol. 1992 Nov;119(4):905–912. doi: 10.1083/jcb.119.4.905. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Liu C. P., Auerbach R. Ontogeny of murine T cells: thymus-regulated development of T cell receptor-bearing cells derived from embryonic yolk sac. Eur J Immunol. 1991 Aug;21(8):1849–1855. doi: 10.1002/eji.1830210811. [DOI] [PubMed] [Google Scholar]
- Paige C. J., Kincade P. W., Ralph P. Murine B cell leukemia line with inducible surface immunoglobulin expression. J Immunol. 1978 Aug;121(2):641–647. [PubMed] [Google Scholar]
- Robertson E., Bradley A., Kuehn M., Evans M. Germ-line transmission of genes introduced into cultured pluripotential cells by retroviral vector. Nature. 1986 Oct 2;323(6087):445–448. doi: 10.1038/323445a0. [DOI] [PubMed] [Google Scholar]
- Russell E. S. Hereditary anemias of the mouse: a review for geneticists. Adv Genet. 1979;20:357–459. [PubMed] [Google Scholar]
- Schaller M. D., Borgman C. A., Cobb B. S., Vines R. R., Reynolds A. B., Parsons J. T. pp125FAK a structurally distinctive protein-tyrosine kinase associated with focal adhesions. Proc Natl Acad Sci U S A. 1992 Jun 1;89(11):5192–5196. doi: 10.1073/pnas.89.11.5192. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Solvason N., Lehuen A., Kearney J. F. An embryonic source of Ly1 but not conventional B cells. Int Immunol. 1991 Jun;3(6):543–550. doi: 10.1093/intimm/3.6.543. [DOI] [PubMed] [Google Scholar]
- Takagaki Y., Nakanishi N., Ishida I., Kanagawa O., Tonegawa S. T cell receptor-gamma and -delta genes preferentially utilized by adult thymocytes for the surface expression. J Immunol. 1989 Mar 15;142(6):2112–2121. [PubMed] [Google Scholar]
- Zachary I., Rozengurt E. Focal adhesion kinase (p125FAK): a point of convergence in the action of neuropeptides, integrins, and oncogenes. Cell. 1992 Dec 11;71(6):891–894. doi: 10.1016/0092-8674(92)90385-p. [DOI] [PubMed] [Google Scholar]
- Zachary I., Sinnett-Smith J., Rozengurt E. Bombesin, vasopressin, and endothelin stimulation of tyrosine phosphorylation in Swiss 3T3 cells. Identification of a novel tyrosine kinase as a major substrate. J Biol Chem. 1992 Sep 25;267(27):19031–19034. [PubMed] [Google Scholar]