RasGRP3 mediates phorbol ester-induced, protein kinase C-independent exocytosis.
RasGRP3 mediates phorbol ester-induced, protein kinase C-independent exocytosis.
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DOI：
10.1016/j.bbrc.2005.02.031
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发表时间：
2005-04
影响因子：
3.1
通讯作者：
N. Ozaki;Y. Miura;Tsutomu Yamada;Y. Kato;Y. Oiso
中科院分区：
文献类型：
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作者：
N. Ozaki;Y. Miura;Tsutomu Yamada;Y. Kato;Y. Oiso
佛波酯通过激活蛋白激酶C(PKC)参与神经递质的释放和激素的分泌。此外，最近有报道以非PKC依赖的方式增加神经递质的释放。然而，胞吐的机制还没有完全阐明。如今，RasGRP家族的成员被发现是与二酰甘油和钙结合的新分子，代表着一类新的鸟嘌呤核苷酸交换因子，可以激活包括Ras和Rap1在内的小GTP酶。在本研究中，我们证明了RasGRP3在内分泌组织中表达，并介导佛波酯诱导的胞吐作用。此外，这一作用可被PKC抑制剂部分阻断，但丝裂原激活的蛋白激酶抑制剂不能，尽管两者都能显著抑制佛波酯诱导的胞外信号调节激酶1/2的磷酸化。这些结果表明RasGRP3参与佛波酯诱导的非PKC非依赖性胞吐作用。
Phorbol esters are involved in neurotransmitter release and hormone secretion via activation of protein kinase C (PKC). In addition, it has been recently reported to enhance neurotransmitter release in a PKC-independent manner. However, the exocytotic machinery is not fully clarified. Nowadays members of the RasGRP family are being identified as novel molecules binding to diacylglycerol and calcium, representing a new class of guanine nucleotide exchange factor that activates small GTPases including Ras and Rap1. In the present study, we demonstrated that RasGRP3 is expressed in endocrine tissues and mediates phorbol ester-induced exocytosis. Furthermore, the effects were partially blocked by PKC inhibitor but not mitogen-activated protein kinase kinase inhibitor, although both significantly suppressed the phorbol ester-induced phosphorylation of extracellular signal-regulated kinase 1/2. These results indicate that RasGRP3 is implicated in phorbol ester-induced, PKC-independent exocytosis.