Requirement for a negative charge at threonine 60 of the FcRγ for complete activation of Syk
Requirement for a negative charge at threonine 60 of the FcRγ for complete activation of Syk
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DOI：
10.1074/jbc.274.33.23068
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发表时间：
1999-08-13
影响因子：
4.8
通讯作者：
Rivera, J
中科院分区：
文献类型：
--
作者：
Swann, PG;Odom, S;Rivera, J
Aggregation of Fc epsilon RI on mast cells results in the phosphorylation of the Fc epsilon RI gamma chain on tyrosine and threonine residues within the immunoreceptor tyrosine-based activation motif, In the present study we sought to identify the site of threonine phosphorylation in Fc epsilon RI gamma and investigate its functional importance. We found that threonine 60 was phosphorylated in vitro and in vivo. Expression of a mutated Fc epsilon RI gamma (T60A), in either Fc epsilon RI gamma-deficient or gamma-null mast cells, resulted in a delay of Fc epsilon RI endocytosis, inhibition of TNF-alpha mRNA production, and inhibition of degranulation but did not affect Fc epsilon RI-induced cell adhesion. Tyrosine phosphorylation of the T60A mutant gamma chain was normal, but Syk phosphorylation was dramatically reduced in these transfectents, This correlated with reduced co-immunoprecipitation of Fc epsilon RI gamma with Syk. Substitution of an aspartic residue for threonine 60 of the Fc epsilon RI gamma reconstituted complete activation of Syk and co-immunoprecipitation of Fc epsilon RI gamma with Syk. We conclude that the negative charge provided by phosphorylation of threonine 60 of the Fc epsilon RI gamma is required for the appropriate interaction and activation of Syk, This is a likely requirement for immunoreceptor tyrosine-based activation motifs involved in Syk activation.
