Walleye dermal sarcoma virus Orf B functions through receptor for activated C kinase (RACK1) and protein kinase C.
Walleye dermal sarcoma virus is a complex retrovirus that is associated with walleye dermal sarcomas that are seasonal in nature. Fall developing tumors contain low levels of spliced accessory gene transcripts A and B, suggesting a role for the encoded proteins, Orf A and Orf B, in oncogenesis. In explanted tumor cells the 35 kDa Orf B accessory protein is localized to the cell periphery in structures similar to focal adhesions and along actin stress fibers. Similar localization was observed in mammalian cells. The cellular protein, receptor for activated C kinase 1 (RACK1), bound Orf B in yeast two-hybrid assays and in cell culture. Sequence analysis of walleye RACK1 demonstrated high conservation to other known RACK1 sequences. RACK1 binds to activated protein kinase C (PKC). Orf B associates with PKCalpha, which is constitutively activated and localized at the membrane. Activated PKC promoted cell survival, proliferation, and increased cell viability in Orf B-expressing cells.
Daniels
Candelaria C
CC
Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO 80523, USA.
Rovnak
Joel
J
Quackenbush
Sandra L
SL
D000595:Amino Acid Sequence; D000818:Animals; D002455:Cell Division / Q000502:physiology; D002460:Cell Line; D004789:Enzyme Activation; D030283:Epsilonretrovirus / Q000737:chemistry* / Q000472:pathogenicity; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D011493:Protein Kinase C / Q000378:metabolism*; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D012192:Retroviridae Infections / Q000821:virology*; D016415:Sequence Alignment; D015398:Signal Transduction; D014412:Tumor Virus Infections / Q000821:virology*; D015854:Up-Regulation; D014764:Viral Proteins / Q000378:metabolism*
D009363:Neoplasm Proteins; C419368:RACK1 protein, human; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface; D014764:Viral Proteins; D011493:Protein Kinase C; D019204:GTP-Binding Proteins