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 cyt oplasmic protein tyrosine kinases (PTKs) and tyrosine-containing seque nces in the cytoplasmic domain of the receptor or an associated subuni t. 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 t ransmit a phagocytic signal in transfected COS-1 cells. Both Fc gamma RI and Fc gamma RIIIA require the gamma subunit for this signaling eve nt. The protein tyrosine kinase Syk dramatically enhances phagocytosis mediated by both these receptors and increases the number of cells ab le 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 r equire the gamma chain for phagocytosis. However, Syk allows phagocyto sis by the nonphagocytic Fc gamma RII receptor Fc gamma RIIB2, which c ontains only a single YXXL sequence, when an additional tyrosine-conta ining sequence, YMTL, is introduced. These studies indicate that the e fficiency of phagocytosis is markedly enhanced by the presence of a sp ecific protein tyrosine kinase. (C) 1995 by The American Society of He matology.