Induction of phagocytosis by a protein tyrosine kinase.
The transmission of extracellular signals to cellular targets by many noncatalytic surface receptors is dependent on interaction between cytoplasmic protein tyrosine kinases (PTKs) and tyrosine-containing sequences in the cytoplasmic domain of the receptor or an associated subunit. Isoforms of each of the three classes of the noncatalytic Fc gamma receptors, Fc gamma RI, Fc gamma RII, and Fc gamma RIII, are able to transmit a phagocytic signal in transfected COS-1 cells. Both Fc gamma RI and Fc gamma RIIIA require the gamma subunit for this signaling event. The protein tyrosine kinase Syk dramatically enhances phagocytosis mediated by both these receptors and increases the number of cells able to mediate phagocytosis. Two gamma chain cytoplasmic YXXL sequences are required for this effect. The action of Syk is less pronounced on the phagocytic Fc gamma RII receptor, Fc gamma RIIA, which does not require the gamma chain for phagocytosis. However, Syk allows phagocytosis by the nonphagocytic Fc gamma RII receptor Fc gamma RIIB2, which contains only a single YXXL sequence, when an additional tyrosine-containing sequence, YMTL, is introduced. These studies indicate that the efficiency of phagocytosis is markedly enhanced by the presence of a specific protein tyrosine kinase.
Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia.
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D000595:Amino Acid Sequence; D000818:Animals; D002461:Cell Line, Transformed; D002522:Chlorocebus aethiops; D004792:Enzyme Precursors / Q000235:genetics / Q000502:physiology*; D047908:Intracellular Signaling Peptides and Proteins; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010587:Phagocytosis / Q000502:physiology*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D017452:Receptors, IgG / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D000072377:Syk Kinase; D014162:Transfection
D004792:Enzyme Precursors; D047908:Intracellular Signaling Peptides and Proteins; D017452:Receptors, IgG; D011993:Recombinant Fusion Proteins; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase