Interaction of p59fyn with interferon-activated Jak kinases.
During IFN alpha stimulation, p59(fyn) associates with the Type I IFNR-associated Tyk-2 kinase in several human hematopoietic cell lines in vivo. This interaction is direct, and is mediated by the SH2 domain in p59(fyn), as shown by binding studies using glutathione-S-transferase fusion proteins and far western blots. Furthermore, in response to IFN alpha-treatment of cells, the SH2 domain of Fyn interacts with the Tyk-2-associated c-cbl proto-oncogene product. In a similar manner, during IFN gamma stimulation, p59(fyn) associates via its SH2 domain with the activated form of the IFN gamma-dependent Jak-2 kinase. These data suggest that p59(fyn) is a common element in IFN alpha and IFN gamma signaling, and is selectively engaged by the Type I or II IFN receptors via specific interactions with distinct Jak kinases.
Uddin
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S
Department of Medicine, University of Illinois at Chicago and West Side Veterans Affairs Hospital, 60607, USA.
Sher
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DA
Alsayed
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Y
Pons
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S
Colamonici
O R
OR
Fish
E N
EN
White
M F
MF
Platanias
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LC
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism; D015153:Blotting, Western; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology; D053613:Janus Kinase 1; D053614:Janus Kinase 2; D019000:Phosphotyrosine / Q000276:immunology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000276:immunology / Q000378:metabolism*; D050721:Proto-Oncogene Proteins c-cbl; D051076:Proto-Oncogene Proteins c-fyn; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D011994:Recombinant Proteins; D015398:Signal Transduction / Q000502:physiology; D053634:TYK2 Kinase; D014407:Tumor Cells, Cultured; D044767:Ubiquitin-Protein Ligases; D018909:src Homology Domains
D000911:Antibodies, Monoclonal; D007370:Interferon Type I; C000715470:MAS1 protein, human; D011506:Proteins; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D019000:Phosphotyrosine; D007371:Interferon-gamma; D050721:Proto-Oncogene Proteins c-cbl; D044767:Ubiquitin-Protein Ligases; D005982:Glutathione Transferase; D011505:Protein-Tyrosine Kinases; C494957:FYN protein, human; C507904:JAK1 protein, human; C507924:JAK2 protein, human; D053613:Janus Kinase 1; D053614:Janus Kinase 2; D051076:Proto-Oncogene Proteins c-fyn; D053634:TYK2 Kinase; C070139:TYK2 protein, human; C067419:CBL protein, human