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  • Original Paper
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Leukocyte-specific adaptor protein Grap2 interacts with hematopoietic progenitor kinase 1 (HPK1) to activate JNK signaling pathway in T lymphocytes

Oncogene volume 20, pages 1703–1714 (2001)Cite this article

Abstract

Immune cell-specific adaptor proteins create various combinations of multiprotein complexes and integrate signals from cell surface receptors to the nucleus, modulating the specificity and selectivity of intracellular signal transduction. Grap2 is a newly identified adaptor protein specifically expressed in lymphoid tissues. This protein shares 40–50% sequence homology in the SH3 and the SH2 domain with Grb2 and Grap. However, the Grap2 protein has a unique 120-amino acid glutamine- and proline-rich domain between the SH2 and C-terminal SH3 domains. The expression of Grap2 is highly restricted to lymphoid organs and T lymphocytes. In order to understand the role of this specific adaptor protein in immune cell signaling and activation, we searched for the Grap2 interacting protein in T lymphocytes. We found that Grap2 interacted with the hematopoietic progenitor kinase 1 (HPK1) in vitro and in Jurkat T cells. The interaction was mediated by the carboxyl-terminal SH3 domain of Grap2 with the second proline-rich motif of HPK1. Coexpression of Grap2 with HPK1 not only increased the kinase activity of HPK1 in the cell, but also had an additive effect on HPK1 mediated JNK activation. Furthermore, over expression of Grap2 and HPK1 induced significant transcriptional activation of c-Jun in the JNK signaling pathway and IL-2 gene reporter activity in stimulated Jurkat T cells. Therefore, our data suggest that the hematopoietic specific proteins Grap2 and HPK1 form a signaling complex to mediate the c-Jun NH2-terminal kinase (JNK) signaling pathway in T cells.

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Acknowledgements

This work was supported in part by a Scientist Development Grant 0030160N from the American Heart Association National and the Basil O'Connor Starter Scholar Research Award from March of Dimes Foundation (to M Liu) and NIH grants RO1-AI42532 and RO1-AI38649 (to T-H Tan).

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Authors and Affiliations

  1. Department of Medical Biochemistry and Genetics, Center for Cancer Biology and Nutrition, Institute of Biosciences and Technology, Texas A&M University System Health Science Center, 2121 W. Holcombe Blvd., Texas, 77030, Houston, TX, USA

    Wenbin Ma, Chunzhi Xia & Mingyao Liu

  2. Department of Immunology, Baylor College of Medicine, 77030, Houston, Texas, TX, USA

    Pin Ling & Tse-Hua Tan

  3. Department of Anatomical Sciences and Neurobiology, School of Medicine, University of Louisville, Louisville, 40202, Kentucky, KY, USA

    Mengsheng Qiu

  4. Shanghai Genomics, Inc., Zhangjiang Hi-Tech Park, Pudong, Shangai 201204, P.R.C.

    Ying Luo

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Ma, W., Xia, C., Ling, P. et al. Leukocyte-specific adaptor protein Grap2 interacts with hematopoietic progenitor kinase 1 (HPK1) to activate JNK signaling pathway in T lymphocytes. Oncogene 20, 1703–1714 (2001). https://doi.org/10.1038/sj.onc.1204224

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  • DOI: https://doi.org/10.1038/sj.onc.1204224

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