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Blood, 15 September 2007, Vol. 110, No. 6, pp. 1730-1738. Prepublished online as a Blood First Edition Paper on May 30, 2007; DOI 10.1182/blood-2007-01-068411. This Article Full Text Full Text (PDF) Supplemental Figure All Versions of this Article: blood-2007-01-068411v1 110/6/1730    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Patrussi, L. Articles by Baldari, C. T. Search for Related Content PubMed PubMed Citation Articles by Patrussi, L. Articles by Baldari, C. T. Related Collections Chemokines, Cytokines, and Interleukins Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CHEMOKINES, CYTOKINES, AND INTERLEUKINS p52Shc is required for CXCR4-dependent signaling and chemotaxis in T cells Laura Patrussi1, Cristina Ulivieri1, Orso Maria Lucherini1, Silvia Rossi Paccani1, Alessandra Gamberucci2, Luisa Lanfrancone3, Pier Giuseppe Pelicci3, and Cosima T. Baldari1 Departments of1 Evolutionary Biology and 2 Physiopathology, University of Siena, Siena; 3 Department of Molecular Oncology, European Institute of Oncology, Milan, Italy ShcA is an important mediator of Ras/MAPK activation in PTK-regulated pathways triggered by surface receptors. This function is subserved by the constitutively expressed p52-kDa isoform. Besides activating Ras, p52Shc couples the TCR to Rho GTPases, and thereby participates in actin cytoskeleton remodeling in T cells. Here we have addressed the potential involvement of p52Shc in T-cell chemotaxis and the role of the phosphorylatable tyrosine residues, YY239/240 and Y317, in this process. We show that CXCR4 engagement by the homeostatic chemokine, SDF-1, results in p52Shc phosphorylation and its assembly into a complex that includes Lck, ZAP-70, and Vav. This process was found to be both Lck and Gi dependent. Expression of p52Shc mutants lacking YY239/240 or Y317, or p52Shc deficiency, resulted in a profound impairment in CXCR4 signaling and SDF-1–dependent chemotaxis, underscoring a crucial role of p52Shc as an early component of the CXCR4 signaling cascade. p52Shc was also found to be required for ligand-dependent CXCR4 internalization independently of tyrosine phosphorylation. Remarkably, CXCR4 engagement promoted phosphorylation of the chain of the TCR/CD3 complex, which was found to be essential for CXCR4 signaling, as well as for SDF-1–dependent receptor endocytosis and chemotaxis, indicating that CXCR4 signals by transactivating the TCR. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. R. Paccani, F. D. Molin, M. Benagiano, D. Ladant, M. M. D'Elios, C. Montecucco, and C. T. Baldari Suppression of T-Lymphocyte Activation and Chemotaxis by the Adenylate Cyclase Toxin of Bordetella pertussis Infect. Immun., July 1, 2008; 76(7): 2822 - 2832. [Abstract] [Full Text] [PDF] F. Finetti, M. Pellegrini, C. Ulivieri, M. T. Savino, E. Paccagnini, C. Ginanneschi, L. Lanfrancone, P. G. Pelicci, and C. T. Baldari The proapoptotic and antimitogenic protein p66SHC acts as a negative regulator of lymphocyte activation and autoimmunity Blood, May 15, 2008; 111(10): 5017 - 5027. [Abstract] [Full Text] [PDF]

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