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Involvement of the adapter protein CRKL in integrin-mediated adhesion

Oncogene volume 18, pages 3343–3353 (1999)Cite this article

Abstract

CRKL, an SH2-SH3-SH3 adapter protein, is one of the major tyrosine phosphoproteins detected in primary leukemic neutrophils from patients with CML. CRKL binds directly to BCR/ABL through its N-terminal SH3 domain, suggesting it may be involved in BCR/ABL signal transduction. However, the biological function of CRKL in either normal or leukemic cells is still largely unknown. In this study, we have examined the effects of overexpressing full length or deletion mutants of CRKL in hematopoietic cell lines. Full length, SH2- and SH3(N)-domain deletion mutants of CRKL were transfected into an interleukin-3-dependent hematopoietic cell line, Ba/F3, and 3 – 5 individual sublines which stably overexpressed each transgene were obtained [Ba/F-CRKL, Ba/F-CRKLΔSH2, and Ba/F-CRKL ΔSH3(N)]. The growth properties of these transfected cells in the presence or absence of IL-3 were not different from mock transfected or untransfected Ba/F3 cells. However, Ba/F3 cells overexpressing full length CRKL, but not deletion mutants of CRKL, were found to have an increase in their ability to bind to fibronectin-coated surfaces. Further, expression of full length, but not ΔSH2- or ΔSH3-CRKL deletion mutants, was found to alter cell morphology on fibronectin-coated plates, an effect which was further enhanced by certain kinds of stress stimuli, such as ionizing radiation. Similar results were obtained when CRKL was transiently overexpressed in Ba/F3 cells, and were also obtained in a second IL-3 dependent hematopoietic cell line, 32Dcl3. Adhesion to fibronectin was blocked by anti-β1 integrin monoclonal antibody, but overexpression of CRKL did not affect surface expression of β1 integrins, nor did it spontaneously induce expression of the β1 integrin `activation' epitope recognized by the 9EG7 monoclonal antibody. These data suggest a role for CRKL in signaling pathways which regulate adhesion to fibronectin.

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Acknowledgements

This work was supported by NIH grants CA36167 and DK560654 (JDG).

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  1. Department of Adult Oncology, Dana-Farber Cancer Institute and Harvard Medical School, 44 Binney Street, Boston, MA 02115, Massachusetts, USA

    Naoki Uemura, Ravi Salgia, Darren S Ewaniuk, Marie-Terese Little & James D Griffin

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Uemura, N., Salgia, R., Ewaniuk, D. et al. Involvement of the adapter protein CRKL in integrin-mediated adhesion. Oncogene 18, 3343–3353 (1999). https://doi.org/10.1038/sj.onc.1202689

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