Crkl is the major tyrosine-phosphorylated protein in neutrophils from patients with chronic myelogenous leukemia.

作者: Brian J. Druker , Conor Heaney , James D. Griffin , John R. Hagopian , Keiko Okuda

DOI: 10.1016/S0021-9258(17)31596-X

关键词: Cancer researchABLChronic myelogenous leukemiaK562 cellsAvian sarcoma virusBiologyCRKLFusion proteinPhiladelphia chromosomeAdapter molecule crk

摘要: The Philadelphia chromosome (Ph1), detected in virtually all cases of chronic myelogenous leukemia (CML), is formed by a reciprocal translocation between 9 and 22 that fuses Bcr-encoded sequences upstream exon 2 c-Abl. This oncogene produces fusion protein, p210bcr-abl, which the Abl tyrosine kinase activity elevated. Using anti-phosphotyrosine immunoblotting, we have compared pattern phosphotyrosine-containing proteins from freshly prepared neutrophils patients stable phase CML to normal controls. only consistent difference was presence 39-kDa tyrosine-phosphorylated protein 18 out neutrophil samples not seen same as assessed two-dimensional also present cell lines expressing including K562 cells. cells source purified identified microsequencing Crkl, an SH2/SH3 adaptor related crk avian sarcoma virus, CT10. A direct interaction Crkl has been shown using yeast two-hybrid screen.

参考文章(30)
Matulonis U, Griffin Jd, Salgia R, Okuda K, Druker B, Interleukin-3 and p210 BCR/ABL activate both unique and overlapping pathways of signal transduction in a factor-dependent myeloid cell line. Experimental Hematology. ,vol. 21, pp. 1460- 1466 ,(1993)
B Druker, K Okuda, U Matulonis, R Salgia, T Roberts, JD Griffin, Tyrosine phosphorylation of rasGAP and associated proteins in chronic myelogenous leukemia cell lines. Blood. ,vol. 79, pp. 2215- 2220 ,(1992) , 10.1182/BLOOD.V79.9.2215.BLOODJOURNAL7992215
Stephan M Feller, Beatrice Knudsen, Hidesaburo Hanafusa, None, c-Abl kinase regulates the protein binding activity of c-Crk. The EMBO Journal. ,vol. 13, pp. 2341- 2351 ,(1994) , 10.1002/J.1460-2075.1994.TB06518.X
P. C. Nowell, A minute chromosome in human chronic granulocytic leukemia Science. ,vol. 132, pp. 1497- ,(1960)
T. Matsuguchi, R. Salgia, M. Hallek, M. Eder, B. Druker, T.J. Ernst, J.D. Griffin, Shc phosphorylation in myeloid cells is regulated by granulocyte macrophage colony-stimulating factor, interleukin-3, and steel factor and is constitutively increased by p210BCR/ABL. Journal of Biological Chemistry. ,vol. 269, pp. 5016- 5021 ,(1994) , 10.1016/S0021-9258(17)37647-0
T.J. Ernst, K.E. Slattery, J.D. Griffin, p210Bcr/Abl and p160v-Abl induce an increase in the tyrosine phosphorylation of p93c-Fes Journal of Biological Chemistry. ,vol. 269, pp. 5764- 5769 ,(1994) , 10.1016/S0021-9258(17)37527-0
D Lu, J Liu, M Campbell, JQ Guo, N Heisterkamp, J Groffen, E Canaani, R Arlinghaus, Tyrosine phosphorylation of P160 BCR by P210 BCR-ABL Blood. ,vol. 82, pp. 1257- 1263 ,(1993) , 10.1182/BLOOD.V82.4.1257.1257
B.J. Druker, M. Neumann, K. Okuda, B.R. Franza, J.D. Griffin, rel Is rapidly tyrosine-phosphorylated following granulocyte-colony stimulating factor treatment of human neutrophils. Journal of Biological Chemistry. ,vol. 269, pp. 5387- 5390 ,(1994) , 10.1016/S0021-9258(17)37699-8