Abstract
Tyrosine kinases are implicated in the growth and differentiation of erythroid cells. Aberrant expression and structural alterations of certain tyrosine kinases, such as erbB and sea, are known to trigger erythroleukemia development. To facilitate our understanding of the signal transduction pathways involved in erythroid differentiation and leukemic transformation, we have applied a recently developed tyrosine kinase profile technique to identify the tyrosine kinases and some novel serine/threonine kinases expressed in normal chicken erythroid progenitor cells that respond to TGFα (TGFα-EB), and erythroblasts transformed by viruses encoding v-erbB (v-erbB-EB) and v-sea (v-sea-EB). Our results reveal that the non-receptor tyrosine kinases, Abl, Fyn, Lyn, Btk and Csk, are expressed in all three cell types. The expression level of Btk, a tyrosine kinase implicated in Bruton's syndrome, is exceptionally high in the erythroblastoid cell line 6C2, transformed by the v-erbB carrying avian erythroblastosis virus, AEV-ES4. We have also uncovered a new STE-20-related serine/threonine kinase, KFC, which is abundantly expressed in both the TGFα-stimulated erythroid progenitor cells and v-sea-transformed erythroblasts. Based on sequence homology of the kinase domain, KFC appears to be the first member of a new subfamily of STE-20-like kinases.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Benedict SH, Maki Y, Vogt PK. Avian retrovirus S13: Properties of the genome and of the transformation-specific protein. Virology 145:154–164;1985.
Beug H, Doederlein G, Freudenstein C, Graf T. Erythroblast cell lines transformed by a temperature-sensitive mutant of avian erythroblastosis virus: A model system to study erythroid differentiation in vitro. J Cell Physiol Suppl 1:195–207;1982.
Beug H, Mullner EW, Hayman MJ. Insights into erythroid differentiation obtained from studies on avian erythroblastosis virus. Curr Opin Cell Biol 6:816–824;1994.
Brown JL, Stowers L, Baer M, Trejo J, Coughlin S, Chant J. Human Ste20 homologue hPAK1 links GTPases to the JNK MAP kinase pathway. Curr Biol 6:598–605;1996.
Carter TH, Kung HJ. Tissue-specific transformation by oncogenic mutants of epidermal growth factor receptor. Crit Rev Oncog 5:389–428;1994.
Downward J, Yarden Y, Mayes E, Scrace G, Totty N, Stockwell P, Ullrich A, Schlessinger J, Waterfield MD. Close similarity of epidermal growth factor receptor and v-erb-B oncogene protein sequences. Nature 307:521–527;1984.
Frohman MA, Dush MK, Martin GR. Rapid production of full length cDNAs from rare transcripts: Amplification using a single gene-specific oligonucleotide primer. Proc Natl Acad Sci USA 85:8998–9002;1988.
Fung YK, Lewis WG, Crittenden LB, Kung HJ. Activation of the cellular oncogene c-erbB by LTR insertion: Molecular basis for induction of erythroblastosis by avian leukosis virus. Cell 33:357–368;1983.
Graf T, Royer-Pokora B, Schubert GE, Beug H. Evidence for the multiple oncogenic potential of cloned leukemia virus: In vivo and in vitro studies with avian erythroblastosis virus. Virology 71:423–433;1976.
Hanks SK, Quinn AM. Protein kinase catalytic domain sequence database: Identification of conserved features of primary structure and classification of family members. Methods Enzymol 200:38–63;1991.
Hayman MJ, Kitchener G, Vogt PK, Beug H. The putative transforming protein of S13 avian erythroblastosis virus is a transmembrane glycoprotein with an associated protein kinase activity. Proc Natl Acad Sci USA 82:8237–8241;1985.
Hayman MJ, Meyer S, Martin F, Steinlein P, Beug H. Self-renewal and differentiation of normal avian erythroid progenitor cells: Regulatory roles of the TGF alpha/c-ErbB and SCF/c-kit receptors. Cell 74:157–169;1993.
Hu MC, Qiu WR, Wang X, Meyer CF, Tan TH. Human HPK1, a novel human hematopoietic progenitor kinase that activates the JNK/SAPK kinase cascade. Genes Dev 10:2251–2264;1996.
Inada T, Iwama A, Sakano S, Ohno M, Sawada K, Suda T. Selective expression of the receptor tyrosine kinase, HTK on human erythroid progenitor cells. Blood 89:2757–2765;1997.
Katz P, Whalen G, Kehrl JH. Differential expression of a novel protein kinase in human B lymphocytes. Preferential localization in the germinal center. J Biol Chem 269:16802–16809;1994.
Kuramochi S, Moriguchi T, Kuida K, Endo U, Semba K, Nishida E, Karasuyama H. LOK is a novel mouse STE-20-like protein kinase that is expressed predominantly in lymphocytes. J Biol Chem 36:22679–22684;1997.
Kuruvilla A, Pielop C, Shearer WT. Platelet-activating factor induces the tyrosine phosphorylation and activation of phospholipase C-gamma 1, Fyn and Lyn kinases, and phosphatidylinositol 3-kinase in a human B cell line. J Immunol 153:5433–5442;1994.
Leberer E, Dignard D, Thomas DY, Whiteway M. The protein kinase homologue Ste20p is required to link the yeast pheromone response G protein subunits to downstream signalling components. EMBO J 11:4815–4824;1993.
Lindberg RA, 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 10:6316–6324;1990.
Manser E, Leung T, Salihuddin H, Zhao ZS, Lim L. A brain serine/threonine protein kinase activated by Cdc42 and Rac1. Nature 367:40–46;1994.
McNiece IK, Langley KE, Zsebo KM. Recombinant human stem cell factor synergises with GM-CSF, G-CSF, IL-3 and epo to stimulate human progenitor cells of the myeloid and erythroid lineages. Exp Hematol 19:226–231;1991.
Nilsen TW, Maroney PA, Goodwin RG, Rottman FM, Crittenden LB, Raines MA, Kung HJ. c-erbB activation in ALV-induced erythroblastosis: Novel RNA processing and promoter insertion result in expression of an amino-truncated EGF receptor. Cell 41:719–726;1985.
Pain B, Melet F, Saez J, Flickinger T, Raines M, Peyrol S, Moscovici C, Mocovici MG, Kung HJ, Jurdic P, Lazarides F, Samarut J. EGF-R as a hemopoietic growth factor receptor: The c-erbB product is present in erythrocytic cells. Cell 65:34–46;1993.
Pombo CM, Bonventre JV, Molnar A, Kryiakis J, Force T. Activation of a human Ste-20-like kinase by oxidant stress defines a novel stress response pathway. EMBO J 17:4537–4546;1996.
Pombo CM, Kehrl JH, Sanchez I, Katz P, Avruch J, Zon LI, Woodgett JR, Force T, Kyriakis JM. Activation of the SAPK pathway by the human STE20 homologue germinal centre kinase. Nature 377:750–754;1995.
Privalsky ML. v-erbA, nuclear hormone receptors, and oncogenesis. Biochim Biophys Acta 1114:51–62;1992.
Rawlings DJ, Witte ON. The Btk subfamily of cytoplasmic tyrosine kinases: Structure, regulation and function. Semin Immunol 7:237–246;1995.
Robinson D, He F, Pretlow T, Kung HJ. A tyrosine kinase profile of prostate carcinoma. Proc Natl Acad Sci USA 93:5958–5962;1996.
Rosenberg N, Witte O. The viral and cellular forms of abl oncogene. Adv Virus Res 35:39–81;1988.
Tung RM, Blenis J. A novel human SPS1/STE20 homologue, KHS, activates Jun N-terminal kinase. Oncogene 14:653–659;1997.
Wessely O, Mellitzer G, von Lindern M, Levitzki A, Gazit A, Ischenko I, Hayman MJ, Beug H. Distinct roles of the receptor tyrosine kinases c-ErbB and c-Kit in regulating the balance between erythroid cell proliferation and differentiation. Cell Growth Differ 8:481–493;1997.
Wu H, Klingmuller U, Acurio A, Hsiao JG, Lodish HF. Functional interaction of erythropoietin and stem cell factor receptors is essential for erythroid colony formation. Proc Natl Acad Sci USA 94:1806–1810;1997.
Wu H, Klingmuller U, Besmer P, Lodish HF. Interaction of the erythropoietin and stem-cell-factor receptors. Nature 377:242–246;1995.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Robinson, D., Chen, HC., Li, D. et al. Tyrosine kinase expression profiles of chicken erythro-progenitor cells and oncogene-transformed erythroblasts. J Biomed Sci 5, 93–100 (1998). https://doi.org/10.1007/BF02258362
Issue Date:
DOI: https://doi.org/10.1007/BF02258362