Correlations among tyrosine phosphorylation of Shc, p72syk, PLC-gamma 1, and [Ca2+]i flux in Fc gamma RIIA signaling.
Tyrosine phosphorylation plays a critical role in Fc gamma RIIA signaling. In a mouse macrophage cell line transfected with human Fc gamma RIIA, cross-linking Fc gamma RIIA led to the transient generation of inositol 1, 4, 5-trisphosphate (IP3), [Ca2+]i flux, and rapid tyrosine phosphorylation of cellular substrates, including Shc, PLC-gamma 1, and a tyrosine kinase p72syk. In addition, tyrosine phosphorylated Fc gamma RIIA was co-precipitated with activated PLC-gamma 1. In contrast, no tyrosine phosphorylation of Shc or PLC-gamma 1 was detected in cells transfected with mutant receptors that failed to trigger [Ca2+]i flux. PMA inhibits both tyrosine phosphorylation of Shc and IP3 production leading to [Ca2+]i flux. However, PMA does not affect tyrosine phosphorylation of PLC-gamma 1 and p72syk. These results suggest that tyrosine phosphorylation of Shc and PLC-gamma 1 is important for the initiation of [Ca2+]i flux, and that activation of protein kinase C may modulate the activity of PLC-gamma 1 through serine/threonine phosphorylation.
Shen
Z
Z
Department of Biochemistry, Mount Sinai School of Medicine, New York, NY 10029.
Lin
C T
CT
Unkeless
J C
JC
D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D004792:Enzyme Precursors / Q000378:metabolism*; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis; D047908:Intracellular Signaling Peptides and Proteins; D007527:Isoenzymes / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D017452:Receptors, IgG / Q000502:physiology*; D000072377:Syk Kinase; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D010738:Type C Phospholipases / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism
D004792:Enzyme Precursors; D047908:Intracellular Signaling Peptides and Proteins; D007527:Isoenzymes; D011518:Proto-Oncogene Proteins; D017452:Receptors, IgG; D014443:Tyrosine; D015544:Inositol 1,4,5-Trisphosphate; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; C000606897:Syk protein, mouse; D010738:Type C Phospholipases; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium