二酰甘油激酶
生物
磷脂酸
细胞生物学
第二信使系统
信号转导
蛋白激酶C
生物化学
受体
胞浆
PLD2型
酶
磷脂
膜
作者
Miguel A. F. Sanjuán,David R. Jones,Manuel Izquierdo,Isabel Mérida
标识
DOI:10.1083/jcb.153.1.207
摘要
Diacylglycerol kinase (DGK) is suggested to attenuate diacylglycerol-induced cell responses through the phosphorylation of this second messenger to phosphatidic acid. Here, we show that DGKalpha, an isoform highly expressed in T lymphocytes, translocates from cytosol to the plasma membrane in response to two different receptors known to elicit T cell activation responses: an ectopically expressed muscarinic type I receptor and the endogenous T cell receptor. Translocation in response to receptor stimulation is rapid, transient, and requires calcium and tyrosine kinase activation. DGKalpha-mediated phosphatidic acid generation allows dissociation of the enzyme from the plasma membrane and return to the cytosol, as demonstrated using a pharmacological inhibitor and a catalytically inactive version of the enzyme. The NH(2)-terminal domain of the protein is shown to be responsible for receptor-induced translocation and phosphatidic acid-mediated membrane dissociation. After examining induction of the T cell activation marker CD69 in cells expressing a constitutively active form of the enzyme, we present evidence of the negative regulation that DGKalpha exerts on diacylglycerol-derived cell responses. This study is the first to describe DGKalpha as an integral component of the signaling cascades that link plasma membrane receptors to nuclear responses.
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