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Blood, 15 October 2006, Vol. 108, No. 8, pp. 2796-2803. Prepublished online as a Blood First Edition Paper on July 6, 2006; DOI 10.1182/blood-2006-04-017434. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-04-017434v1 108/8/2796    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 Han, Y. Articles by Lai, R. Search for Related Content PubMed PubMed Citation Articles by Han, Y. Articles by Lai, R. Related Collections Neoplasia Oncogenes and Tumor Suppressors Signal Transduction Free Research Articles Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Loss of SHP1 enhances JAK3/STAT3 signaling and decreases proteosome degradation of JAK3 and NPM-ALK in ALK+ anaplastic large-cell lymphoma Yajun Han, Hesham M. Amin, Bevin Franko, Christine Frantz, Xinzhe Shi, and Raymond Lai From the Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Canada; and Department of Hematopathology, the University of Texas M. D. Anderson Cancer Center, Houston. Previous studies showed that most cases of ALK+ anaplastic large-cell lymphoma (ALK+ALCL) do not express SHP1, a tyrosine phosphatase and an important negative regulator for cellular signaling pathways such as that of JAK/STAT. To fully assess the biologic significance of loss of SHP1 in ALK+ALCL, we transfected SHP1 plasmids into 2 SHP1-, ALK+ALCL cell lines, Karpas 299 and SU-DHL-1. After 24 hours of transfection, pJAK3 and pSTAT3 were decreased, and these changes correlated with down-regulation of STAT3 downstream targets including cyclin D3, mcl-1, and bcl-2. Expression of SHP1 in these 2 cell lines also resulted in marked decreases in the protein levels of JAK3 and NPM-ALK, and these effects were reversible by proteosome inhibitor MG132. Conversely, when SHP1 expression in SUP-M2 (a SHP1+ ALK+ALCL cell line) was inhibited using siRNA, pSTAT3, pJAK3, JAK3, and NPM-ALK were all up-regulated. Coimmunoprecipitation studies showed that SHP1 was physically associated with JAK3 and NPM-ALK. SHP1 expression in Karpas 299 and SU-DHL-1 led to significant G1 cell cycle arrest but not apoptosis. To conclude, loss of SHP1 contributes to the pathogenesis of ALK+ALCL by 2 mechanisms: (1) it leaves the tyrosine phosphorylation and activation of JAK3/STAT3 unchecked and (2) it decreases proteosome degradation of JAK3 and NPM-ALK. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: ALK-mediated oncogenesis: mechanisms that matter Stephan W. Morris Blood 2006 108: 2500-2501. [Full Text] [PDF] This article has been cited by other articles: M. K. Pandey, B. Sung, K. S. Ahn, and B. B. Aggarwal Butein Suppresses Constitutive and Inducible Signal Transducer and Activator of Transcription (STAT) 3 Activation and STAT3-Regulated Gene Products through the Induction of a Protein Tyrosine Phosphatase SHP-1 Mol. Pharmacol., March 1, 2009; 75(3): 525 - 533. [Abstract] [Full Text] [PDF] F. Wu, P. Wang, L. C. Young, R. Lai, and L. 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