Critical Role for Endocytosis in the Regulation of Signaling by the Kaposi's Sarcoma-Associated Herpesvirus K1 Protein
| Autor: | Blossom Damania, Christine C. Tomlinson |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
media_common.quotation_subject
Blotting Western Green Fluorescent Proteins Immunoblotting education Immunology Syk Biology medicine.disease_cause Endocytosis Microbiology Phosphatidylinositol 3-Kinases Viral Proteins Virology medicine Humans Immunoprecipitation Syk Kinase Gammaherpesvirinae Amino Acid Sequence Kaposi's sarcoma-associated herpesvirus Internalization PI3K/AKT/mTOR pathway media_common B-Lymphocytes Intracellular Signaling Peptides and Proteins Protein-Tyrosine Kinases Virus Internalization medicine.disease biology.organism_classification Molecular biology Virus-Cell Interactions Cell biology Enzyme Activation Microscopy Fluorescence Insect Science Herpesvirus 8 Human Primary effusion lymphoma Signal transduction HeLa Cells Signal Transduction |
| Zdroj: | Journal of Virology. 82:6514-6523 |
| ISSN: | 1098-5514 0022-538X |
| DOI: | 10.1128/jvi.02637-07 |
| Popis: | Kaposi's sarcoma-associated herpesvirus (KSHV) is a member of the gammaherpesvirus family. KSHV is the etiologic agent of Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman's disease. The first open reading frame of the KSHV genome encodes a type 1 transmembrane glycoprotein named K1. K1 is structurally similar to the B-cell receptor (BCR), and its cytoplasmic tail contains an immunoreceptor tyrosine-based activation motif that can activate Syk kinase and the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. Recent evidence suggests that receptor signaling occurs not only at the cell membrane, but from intracellular compartments as well. We have found that K1 is internalized in a clathrin-dependent manner, and efficient internalization is coupled to its signaling function. Once internalized, K1 traffics from the early endosome to the recycling endosome. Interestingly, blocking K1's activation of Syk and PI3K prevents K1 from internalizing. We have also found that blocking clathrin-mediated endocytosis prevents downstream signaling by K1. These results strongly suggest that internalization of K1 is intimately associated with normal signaling. When K1 internalization was examined in B lymphocytes, we found that K1 cointernalized with the BCR. Altogether, these results suggest that K1's signaling function is tightly coupled to its internalization. |
| Databáze: | OpenAIRE |
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