Differential regulation of interleukin 5-stimulated signaling pathways by dynamin.
Through the yeast two-hybrid screen we have identified dynamin-2 as a molecule that interacts with the alpha 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.
Division of Allergy and Immunology, Department of Medicine, National Jewish Medical and Research Center, Denver, Colorado 80206, USA.
Magdalena M
MM
Gorska
Osman
O
Cen
Qiaoling
Q
Liang
Susan J
SJ
Stafford
Rafeul
R
Alam
D049109:Cell Proliferation; D002470:Cell Survival; D034285:Dynamin II / Q000737:chemistry / Q000378:metabolism*; D004705:Endocytosis; D005786:Gene Expression Regulation; D006801:Humans; D015848:Interleukin-5 / Q000096:biosynthesis* / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D008954:Models, Biological; D015398:Signal Transduction; D014443:Tyrosine / Q000737:chemistry
D015848:Interleukin-5; D014443:Tyrosine; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D034285:Dynamin II