Coupling between p210bcr-abl and Shc and Grb2 adaptor proteins in hematopoietic cells permits growth factor receptor-independent link to ras activation pathway

doi:10.1084/jem.179.1.167

This Article

	Full Text (PDF)
	Alert me when this article is cited
	Citation Map

Services

	Email this article
	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new content in the JEM
	Download to citation manager

Citing Articles

	Citing Articles via HighWire
	Citing Articles via CrossRef
	Citing Articles via Google Scholar

Google Scholar

	Articles by Tauchi, T.
	Articles by Broxmeyer, H. E.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Tauchi, T.
	Articles by Broxmeyer, H. E.


Social Bookmarking

	What's this?

ARTICLES

Coupling between p210bcr-abl and Shc and Grb2 adaptor proteins in hematopoietic cells permits growth factor receptor-independent link to ras activation pathway

T Tauchi, HS Boswell, D Leibowitz and HE Broxmeyer
Department of Medicine (Hematology/Oncology), Indiana University School of Medicine, Indianapolis 46202.

Enforced expression of p210bcr-abl transforms interleukin 3 (IL-3)- dependent hematopoietic cell lines to growth factor-independent proliferation. It has been demonstrated that nonreceptor tyrosine kinase oncogenes may couple to the p21ras pathway to exert their transforming effect. In particular, p210bcr-abl was recently found to effect p21ras activation in hematopoietic cells. In this context, experiments were performed to evaluate a protein signaling pathway by which p210bcr-abl might regulate p21ras. It was asked whether Shc p46/p52, a protein containing a src-homology region 2 (SH2) domain, and known to function upstream from p21ras, might form specific complexes with p210bcr-abl and thus, possibly alter p21ras activity by coupling to the guanine nucleotide exchange factor (Sos/CDC25) through the Grb2 protein-Sos complex. This latter complex has been previously demonstrated to occur ubiquitously. We found that p210bcr-abl formed a specific complex with Shc and with Grb2 in three different murine cell lines transfected with a p210bcr-abl expression vector. There appeared to be a higher order complex containing Shc, Grb2, and bcr-abl proteins. In contrast to p210bcr-abl transformed cells, in which there was constitutive tight association between Grb2 and Shc, binding between Grb2 and Shc was Steel factor (SLF)-dependent in a SLF- responsive, nontransformed parental cell line. The SLF-dependent association between Grb2 and Shc in nontransformed cells involved formation of a complex of Grb2 with c-kit receptor after SLF treatment. Thus, p210bcr-abl appears to function in a hematopoietic p21ras activation pathway to allow growth factor-independent coupling between Grb2, which exists in a complex with the guanine nucleotide exchange factor (Sos), and p21ras. Shc may not be required for Grb2-c-kit interaction, because it fails to bind strongly to c-kit.
Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Add to Reddit Reddit Add to Technorati Technorati What's this?

This article has been cited by other articles:

Unwin, R. D., Sternberg, D. W., Lu, Y., Pierce, A., Gilliland, D. G., Whetton, A. D. (2005). Global Effects of BCR/ABL and TEL/PDGFR{beta} Expression on the Proteome and Phosphoproteome: IDENTIFICATION OF THE RHO PATHWAY AS A TARGET OF BCR/ABL. J. Biol. Chem. 280: 6316-6326 [Abstract] [Full Text]
Lennartsson, J., Jelacic, T., Linnekin, D., Shivakrupa, R. (2005). Normal and Oncogenic Forms of the Receptor Tyrosine Kinase Kit. Stem Cells 23: 16-43 [Abstract] [Full Text]
Goldman, J. M., Melo, J. V. (2003). Chronic Myeloid Leukemia -- Advances in Biology and New Approaches to Treatment. NEJM 349: 1451-1464 [Full Text]
Tauchi, T., Nakajima, A., Sashida, G., Shimamoto, T., Ohyashiki, J. H., Abe, K., Yamamoto, K., Ohyashiki, K. (2002). Inhibition of Human Telomerase Enhances the Effect of the Tyrosine Kinase Inhibitor, Imatinib, in BCR-ABL-positive Leukemia Cells. Clin. Cancer Res. 8: 3341-3347 [Abstract] [Full Text]
Ptasznik, A., Urbanowska, E., Chinta, S., Costa, M. A., Katz, B. A., Stanislaus, M. A., Demir, G., Linnekin, D., Pan, Z. K., Gewirtz, A. M. (2002). Crosstalk Between BCR/ABL Oncoprotein and CXCR4 Signaling through a Src Family Kinase in Human Leukemia Cells. JEM 196: 667-678 [Abstract] [Full Text]
Ho, J. M.-Y., Nguyen, M. H.-H., Dierov, J. K., Badger, K. M., Beattie, B. K., Tartaro, P., Haq, R., Zanke, B. W., Carroll, M. P., Barber, D. L. (2002). TEL-JAK2 constitutively activates the extracellular signal-regulated kinase (ERK), stress-activated protein/Jun kinase (SAPK/JNK), and p38 signaling pathways. Blood 100: 1438-1448 [Abstract] [Full Text]
Wolff, N. C., Ilaria, R. L. Jr (2001). Establishment of a murine model for therapy-treated chronic myelogenous leukemia using the tyrosine kinase inhibitor STI571. Blood 98: 2808-2816 [Abstract] [Full Text]
Gelfanov, V. M., Burgess, G. S., Litz-Jackson, S., King, A. J., Marshall, M. S., Nakshatri, H., Boswell, H. S. (2001). Transformation of interleukin-3-dependent cells without participation of Stat5/bcl-xL: cooperation of akt with raf/erk leads to p65 nuclear factor {kappa}B-mediated antiapoptosis involving c-IAP2. Blood 98: 2508-2517 [Abstract] [Full Text]
Laurent, E., Talpaz, M., Kantarjian, H., Kurzrock, R. (2001). The BCR Gene and Philadelphia Chromosome-positive Leukemogenesis. Cancer Res. 61: 2343-2355 [Full Text]
Coutinho, S., Jahn, T., Lewitzky, M., Feller, S., Hutzler, P., Peschel, C., Duyster, J. (2000). Characterization of Grb4, an adapter protein interacting with Bcr-Abl. Blood 96: 618-624 [Abstract] [Full Text]
Hromas, R., Cripe, L., Hangoc, G., Cooper, S., Broxmeyer, H. E. (2000). The Exodus subfamily of CC chemokines inhibits the proliferation of chronic myelogenous leukemia progenitors. Blood 95: 1506-1508 [Abstract] [Full Text]
Bonati, A., Carlo-Stella, C., Lunghi, P., Albertini, R., Pinelli, S., Migliaccio, E., Sammarelli, G., Savoldo, B., Tabilio, A., Dall’Aglio, P. P., Pelicci, P. G. (2000). Selective Expression and Constitutive Phosphorylation of SHC Proteins in the CD34+ Fraction of Chronic Myelogenous Leukemias. Cancer Res. 60: 728-732 [Abstract] [Full Text]
Cong, F., Yuan, B., Goff, S. P. (1999). Characterization of a Novel Member of the DOK Family That Binds and Modulates Abl Signaling. Mol. Cell. Biol. 19: 8314-8325 [Abstract] [Full Text]
Carlo-Stella, C., Regazzi, E., Sammarelli, G., Colla, S., Garau, D., Gazit, A., Savoldo, B., Cilloni, D., Tabilio, A., Levitzki, A., Rizzoli, V. (1999). Effects of the Tyrosine Kinase Inhibitor AG957 and an Anti-Fas Receptor Antibody on CD34+ Chronic Myelogenous Leukemia Progenitor Cells. Blood 93: 3973-3982 [Abstract] [Full Text]
LaMontagne, K. R. Jr., Hannon, G., Tonks, N. K. (1998). Protein tyrosine phosphatase PTP1B suppresses p210 bcr-abl-induced transformation of Rat-1 fibroblasts and promotes differentiation of K562 cells. Proc. Natl. Acad. Sci. USA 95: 14094-14099 [Abstract] [Full Text]
Pear, W. S., Miller, J. P., Xu, L., Pui, J. C., Soffer, B., Quackenbush, R. C., Pendergast, A. M., Bronson, R., Aster, J. C., Scott, M. L., Baltimore, D. (1998). Efficient and Rapid Induction of a Chronic Myelogenous Leukemia-Like Myeloproliferative Disease in Mice Receiving P210 bcr/abl-Transduced Bone Marrow. Blood 92: 3780-3792 [Abstract] [Full Text]
Hallek, M., Leif Bergsagel, P., Anderson, K. C. (1998). Multiple Myeloma: Increasing Evidence for a Multistep Transformation Process. Blood 91: 3-21 [Full Text]
Blaikie, P. A., Fournier, E., Dilworth, S. M., Birnbaum, D., Borg, J.-P., Margolis, B. (1997). The Role of the Shc Phosphotyrosine Interaction/Phosphotyrosine Binding Domain and Tyrosine Phosphorylation Sites in Polyoma Middle T Antigen-mediated Cell Transformation. J. Biol. Chem. 272: 20671-20677 [Abstract] [Full Text]
Bhat, A., Kolibaba, K., Oda, T., Ohno-Jones, S., Heaney, C., Druker, B. J. (1997). Interactions of CBL with BCR-ABL and CRKL in BCR-ABL-transformed Myeloid Cells. J. Biol. Chem. 272: 16170-16175 [Abstract] [Full Text]
Tauchi, T., Miyazawa, K., Feng, G.-S., Broxmeyer, H. E., Toyama, K. (1997). A Coiled-coil Tetramerization Domain of BCR-ABL Is Essential for the Interactions of SH2-containing Signal Transduction Molecules. J. Biol. Chem. 272: 1389-1394 [Abstract] [Full Text]
Heaney, C., Kolibaba, K., Bhat, A., Oda, T., Ohno, S., Fanning, S., Druker, B. J. (1997). Direct Binding of CRKL to BCR-ABL Is Not Required for BCR-ABL Transformation. Blood 89: 297-306 [Abstract] [Full Text]
Senechal, K., Halpern, J., Sawyers, C. L. (1996). The CRKL Adaptor Protein Transforms Fibroblasts and Functions in Transformation by the BCR-ABL Oncogene. J. Biol. Chem. 271: 23255-23261 [Abstract] [Full Text]
Raffel, G. D., Parmar, K., Rosenberg, N. (1996). In Vivo Association of v-Abl with Shc Mediated by a Non-phosphotyrosine-dependent SH2 Interaction. J. Biol. Chem. 271: 4640-4645 [Abstract] [Full Text]
Thomas, D., Patterson, S. D., Bradshaw, R. A. (1995). Src Homologous and Collagen (Shc) Protein Binds to F-actin and Translocates to the Cytoskeleton upon Nerve Growth Factor Stimulation in PC12 Cells. J. Biol. Chem. 270: 28924-28931 [Abstract] [Full Text]
Owen-Lynch, P. J., Wong, A. K. Y., Whetton, A. D. (1995). v-Abl-mediated Apoptotic Suppression Is Associated with SHC Phosphorylation without Concomitant Mitogen-activated Protein Kinase Activation. J. Biol. Chem. 270: 5956-5962 [Abstract] [Full Text]
Tauchi, T., Feng, G.-S., Shen, R., Hoatlin, M., Bagby, G. C. Jr., Kabat, D., Lu, L., Broxmeyer, H. E. (1995). Involvement of SH2-containing Phosphotyrosine Phosphatase Syp in Erythropoietin Receptor Signal Transduction Pathways. J. Biol. Chem. 270: 5631-5635 [Abstract] [Full Text]
Nguyen, M. H.-H., Ho, J. M.-Y., Beattie, B. K., Barber, D. L. (2001). TEL-JAK2 Mediates Constitutive Activation of the Phosphatidylinositol 3'-Kinase/Protein Kinase B Signaling Pathway. J. Biol. Chem. 276: 32704-32713 [Abstract] [Full Text]