The small 11-kDa protein from B19 parvovirus binds growth factor receptor-binding protein 2 in vitro in a Src homology 3 domain/ligand-dependent manner.
The small 11-kDa proteins of B19 parvovirus contain three proline-rich regions which conform to consensus Src homology 3 (SH3) ligand sequences present in signaling molecules within the cell. We have shown that the B19 11-kDa proteins specifically interact with the growth factor receptor-binding protein 2 (Grb2) in vitro. Mutation of prolines within one of the three SH3 ligand-like sequences decreases the binding of B19 11-kDa proteins to Grb2, suggesting that the proline-rich region is involved in the B19 11-kDa/Grb2 interaction. Therefore, the B19 11-kDa proteins may function to alter Grb2-mediated signaling by disrupting SH3 domain/ligand interactions. These results implicate the 11-kDa proteins in B19 pathogenesis through perturbation of normal cellular signaling pathways.
Fan
M M
MM
Graduate Program in Neuroscience, Kinsmen Laboratory of Neurological Research, University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC V6T 1Z3, Canada.
Tamburic
L
L
Shippam-Brett
C
C
Zagrodney
D B
DB
Astell
C R
CR
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D026481:Blotting, Far-Western; D019556:COS Cells; D002460:Cell Line; D002522:Chlorocebus aethiops; D051380:GRB2 Adaptor Protein; D015870:Gene Expression; D017930:Genes, Reporter; D005982:Glutathione Transferase / Q000235:genetics; D049452:Green Fluorescent Proteins; D006801:Humans; D008024:Ligands; D008164:Luminescent Proteins / Q000235:genetics; D008969:Molecular Sequence Data; D008970:Molecular Weight; D016732:Parvovirus B19, Human / Q000378:metabolism*; D011392:Proline; D011506:Proteins / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics; D017361:Viral Nonstructural Proteins / Q000378:metabolism*; D018909:src Homology Domains
D048868:Adaptor Proteins, Signal Transducing; D051380:GRB2 Adaptor Protein; C495948:GRB2 protein, human; D008024:Ligands; D008164:Luminescent Proteins; D011506:Proteins; D011993:Recombinant Fusion Proteins; D017361:Viral Nonstructural Proteins; D049452:Green Fluorescent Proteins; D011392:Proline; D005982:Glutathione Transferase