Xu R, Seger R, Pecht I
Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel.
J Immunol. 1999 Aug 1;163(3):1110-4.
The protein tyrosine kinase Syk is an essential element in several cascades coupling Ag receptors to cell responses. Syk and the mitogen-activated protein kinase extracellular signal-regulated kinase 1 (ERK1) were found to form a tight complex in both resting and Ag-stimulated rat mucosal-type mast cells (rat basophilic leukemia 2H3 cell line RBL-2H3). A direct serine phosphorylation and activation of Syk by ERK was observed in in vitro experiments. Moreover the mitogen-activated protein kinase/extracellular signal-regulated protein kinase (ERK) kinase (MEK) inhibitors markedly decreased the Ag-induced phosphorylation of the tyrosyl residues of Syk and its activation as well as suppressed the degranulation of the cells. These results suggest a positive feedback regulation of Syk by ERK in the cascade coupling the type 1 Fc epsilon receptor to the secretory response of mast cells; hence, the existence of a novel type of cross-talk between protein serine/threonine kinases and protein tyrosine kinases is suggested.
蛋白酪氨酸激酶Syk是将抗原受体与细胞反应偶联的多个级联反应中的关键元件。在静息和抗原刺激的大鼠黏膜型肥大细胞（大鼠嗜碱性白血病2H3细胞系RBL - 2H3）中，Syk与丝裂原活化蛋白激酶细胞外信号调节激酶1（ERK1）形成紧密复合物。体外实验观察到ERK对Syk进行直接的丝氨酸磷酸化并激活。此外，丝裂原活化蛋白激酶/细胞外信号调节蛋白激酶（ERK）激酶（MEK）抑制剂显著降低抗原诱导的Syk酪氨酸残基磷酸化及其激活，同时抑制细胞脱颗粒。这些结果表明，在将Ⅰ型Fcε受体与肥大细胞分泌反应偶联的级联反应中，ERK对Syk存在正反馈调节；因此，提示蛋白丝氨酸/苏氨酸激酶与蛋白酪氨酸激酶之间存在一种新型的相互作用。
