Nuclear Translocation of Crk Adaptor Proteins by the Influenza A Virus NS1 Protein.
The non-structural protein-1 (NS1) of many influenza A strains, especially those of avian origin, contains an SH3 ligand motif, which binds tightly to the cellular adaptor proteins Crk (Chicken tumor virus number 10 (CT10) regulator of kinase) and Crk-like adapter protein (CrkL). This interaction has been shown to potentiate NS1-induced activation of the phosphatidylinositol 3-kinase (PI3K), but additional effects on the host cell physiology may exist. Here we show that NS1 can induce an efficient translocation of Crk proteins from the cytoplasm into the nucleus, which results in an altered pattern of nuclear protein tyrosine phosphorylation. This was not observed using NS1 proteins deficient in SH3 binding or engineered to be exclusively cytoplasmic, indicating a physical role for NS1 as a carrier in the nuclear translocation of Crk. These data further emphasize the role of Crk proteins as host cell interaction partners of NS1, and highlight the potential for host cell manipulation gained by a viral protein simply via acquiring a short SH3 binding motif.
Department of Virology, University of Helsinki and Helsinki University Hospital, 00014 Helsinki, Finland. leena.ylosmaki@helsinki.fi.
Leena
L
Ylösmäki
Department of Virology, University of Helsinki and Helsinki University Hospital, 00014 Helsinki, Finland. riku.fagerlund@helsinki.fi.
Riku
R
Fagerlund
Department of Virology, University of Helsinki and Helsinki University Hospital, 00014 Helsinki, Finland. inka.kuisma@helsinki.fi.
Inka
I
Kuisma
Department of Virology, University of Turku, 20520 Turku, Finland and Virology Unit, Department of Infectious Disease Surveillance and Control, National Institute for Health and Welfare (THL), 00300 Helsinki, Finland. ilkka.julkunen@utu.fi.
Ilkka
I
Julkunen
Department of Virology, University of Helsinki and Helsinki University Hospital, 00014 Helsinki, Finland. kalle.saksela@helsinki.fi.
Kalle
K
Saksela
D021581:Active Transport, Cell Nucleus; D002460:Cell Line; D054884:Host-Pathogen Interactions; D006801:Humans; D009980:Influenza A virus / Q000502:physiology; D007251:Influenza, Human / Q000378:metabolism / Q000821:virology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D050737:Proto-Oncogene Proteins c-crk / Q000378:metabolism*; D017361:Viral Nonstructural Proteins / Q000737:chemistry / Q000378:metabolism*; D018909:src Homology Domains
C085820:INS1 protein, influenza virus; D050737:Proto-Oncogene Proteins c-crk; D017361:Viral Nonstructural Proteins; D019869:Phosphatidylinositol 3-Kinases
Crk; NS1; SH3 domain; influenza A virus; virus-host interaction