SYK PROTEIN-TYROSINE KINASE REGULATES FC RECEPTOR GAMMA-CHAIN-MEDIATED TRANSPORT TO LYSOSOMES

B- and T-cell receptors, as well as most Fe receptors (FcR), are part of a large family of membrane proteins named immunoreceptors and are e xpressed on all cells of the immune system, Immunoreceptors' biologica l functions rely on two of their fundamental attributes: signal transd uction and internalization. The signals required for these two functio ns are present in the chains associated with immunoreceptors, within c onserved amino acid motifs called immunoreceptor tyrosine-based activa tion motifs (ITAMs), We have examined the role of the protein tyrosine kinase (PTK) syk, a critical effector of immunoreceptor-mediated cell signalling through ITAMs, in FcR-associated gamma-chain internalizati on and lysosomal targeting. A point mutation in the immunoreceptor-ass ociated gamma-chain ITAM affecting syk activation, as well as overexpr ession of a syk dominant negative mutant, inhibited signal transductio n without affecting receptor coated-pit localization or internalizatio n. In contrast, blocking of gamma-chain-mediated syk activation impair ed FcR transport from endosomes to lysosomes and selectively inhibited the presentation of certain T-cell epitopes, Therefore, activation of the PTK syk is dispensable for receptor internalization, but necessar y for cell signalling and for gamma-chain-mediated FcR delivery to lys osomes.