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syk protein tyrosine kinase regulates Fc receptor γ‐chain‐mediated transport to lysosomes
Author(s) -
Bonnerot Christian,
Briken Volker,
Brachet Valérie,
Lankar Danielle,
Cassard Sylvanie,
Jabri Bana,
Amigorena Sebastian
Publication year - 1998
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/17.16.4606
Subject(s) - biology , syk , receptor tyrosine kinase , microbiology and biotechnology , tyrosine kinase , receptor protein tyrosine kinases , proto oncogene tyrosine protein kinase src , tropomyosin receptor kinase c , receptor , platelet derived growth factor receptor , kinase , biochemistry , signal transduction , growth factor
B‐ and T‐cell receptors, as well as most Fc receptors (FcR), are part of a large family of membrane proteins named immunoreceptors and are expressed on all cells of the immune system. Immunoreceptors' biological functions rely on two of their fundamental attributes: signal transduction and internalization. The signals required for these two functions are present in the chains associated with immunoreceptors, within conserved amino acid motifs called immunoreceptor tyrosine‐based activation 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 γ‐chain internalization and lysosomal targeting. A point mutation in the immunoreceptor‐associated γ‐chain ITAM affecting syk activation, as well as overexpression of a syk dominant negative mutant, inhibited signal transduction without affecting receptor coated‐pit localization or internalization. In contrast, blocking of γ‐chain‐mediated syk activation impaired 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 necessary for cell signalling and for γ‐chain‐mediated FcR delivery to lysosomes.