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J. Biol. Chem., Vol. 281, Issue 20, 14429-14439, May 19, 2006

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Differential Regulation of Interleukin 5-stimulated Signaling Pathways by Dynamin^*

Magdalena M. Gorska, Osman Cen, Qiaoling Liang, Susan J. Stafford, and Rafeul Alam¹

From the Division of Allergy and Immunology, Department of Medicine, National Jewish Medical and Research Center, Denver, Colorado 80206 and the Division of Allergy and Immunology, Department of Medicine, University of Texas Medical Branch, Galveston, Texas 77555

Through the yeast two-hybrid screen we have identified dynamin-2 as a molecule that interacts with the subunit of the interleukin (IL) 5 receptor. Dynamin-2 is a GTPase that is critical for endocytosis. We have shown that dynamin-2 interacts with the IL-5 receptor-associated tyrosine kinases, Lyn and JAK2, in eosinophils. Tyrosine phosphorylation of dynamin is markedly enhanced upon IL-5 stimulation. The inhibition of tyrosine kinases results in complete abolition of ligand-induced receptor endocytosis. Inhibition of dynamin by a dominant-negative mutant or by small interfering RNA results in enhancement of IL-5-stimulated ERK1/2 signaling and cell proliferation. In contrast, the absence of a functional dynamin does not affect STAT5 or AKT phosphorylation or cell survival. Thus, we have identified specific functions for dynamin in the IL-5 signaling pathway and demonstrated its role in receptor endocytosis and termination of the ERK1/2 signaling pathway.

Received for publication, November 28, 2005 , and in revised form, March 20, 2006.

^* This work was supported by National Institutes of Health Grants RO1 AI50179, AI059719, and AI68088. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence should be addressed: 1400 Jackson St., Denver, CO 80206. Tel.: 303-270-2907; Fax: 303-398-1225; E-mail: alamr{at}njc.org.

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