DYNAMICS AND ORGANIZATION OF MAP KINASE SIGNAL PATHWAYS
DYNAMICS AND ORGANIZATION OF MAP KINASE SIGNAL PATHWAYS
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DOI：
10.1002/mrd.1080420416
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发表时间：
1995-12-01
影响因子：
2.5
通讯作者：
MATSUMOTO, K
中科院分区：
文献类型：
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作者：
ERREDE, B;CADE, RM;MATSUMOTO, K
在芽殖酵母，酿酒酵母，四个独立的，但结构相关的丝裂原活化蛋白激酶（MAPK）激活途径是已知的。最好的理解这些调节交配。信息素与受体的结合告知细胞交配伴侣的接近并诱导分化为交配能力状态。介导该信号的MAPK激活级联由Ste 11（MEK激酶[MEKK]），Ste 7（MAPK/ERK激酶[MEK]）和冗余MAPK相关的Fus 3和Kss 1酶组成。另一条MAPK活化途径对细胞完整性很重要，并调节细胞壁的构建。该级联由Bck 1（MEKK），冗余Mkk 1和Mkk 2酶（MEK）和Mpk 1（MAPK）组成。我们利用这两条途径来研究MAPK激活级联的协调和信号传递的保真度。两条证据表明，在交配分化过程中，交配和细胞完整性途径的活动是协调的。首先，Mpk 1缺陷的细胞在它们对信息素作出交配投射时容易裂解。第二，Mpk 1激活信息素诱导过程中与投影形成相一致。我们仍然不知道这种协调的机制。我们的工作模型是，投影形成产生一个移动的第二信使激活的细胞完整性pathway.分析的STE 7突变给了我们一些意想不到的，但重要的见解参数的保真度的信号传输的重要。Ste 7变体在位置368处具有丝氨酸至脯氨酸的取代。Ste 7-P-368具有比野生型酶更高的基础活性，但其功能仍然需要Stell。此外，脯氨酸取代使得变体能够传递来自酵母中表达的哺乳动物Raf的信号。这种新的活性表明Ste 7-P-368在与MEKK的相互作用中固有地比Ste 7更宽容。然而，Ste 7-P-368在细胞完整性途径中的交叉功能仅在其高度过量产生或Ste 5缺失时发生。这种行为表明，Ste 5，这已被提出是一个系链的激酶在交配途径，有助于Ste 7特异性和保真度的信号传输。(C)1995年Wiley-Liss，Inc.
In the budding yeast, Saccharomyces cerevisiae, four separate but structurally related mitogen-activated protein kinase (MAPK) activation pathways are known. The best understood of these regulates mating. Pheromone binding to receptor informs cells of the proximity of a mating partner and induces differentiation to a mating competent state. The MAPK activation cascade mediating this signal is made up of Ste11 (a MEK kinase [MEKK]), Ste7 (a MAPK/ERK kinase [MEK]), and the redundant MAPK-related Fus3 and Kss1 enzymes. Another MAPK activation pathway is important for cell integrity and regulates cell wall construction. This cascade consists of Bck1 (a MEKK), the redundant Mkk1 and Mkk2 enzymes (MEKs), and Mpk1 (a MAPK). We exploited these two pathways to learn about the coordination and signal transmission fidelity of MAPK activation cascades.Two lines of evidence suggest that the activities of the mating and cell integrity pathways are coordinated during mating differentiation. First, cells deficient in Mpk1 are susceptible to lysis when they make a mating projection in response to pheromone. Second, Mpk1 activation during pheromone induction coincides with projection formation. The mechanism underlying this coordination is still unknown to us. Our working model is that projection formation generates a mobile second messenger for activation of the cell integrity pathway.Analysis of a STE7 mutation gave us some unanticipated but important insights into parameters important for fidelity of signal transmission. The Ste7 variant has a serine to proline substitution at position 368. Ste7-P-368 has higher basal activity than the wild-type enzyme but still requires Stell for its function. Additionally, the proline substitution enables the variant to transmit the signal from mammalian Raf expressed in yeast. This novel activity suggests that Ste7-P-368 i, inherently more permissive than Ste7 in its interactions with MEKKs. Yet, Ste7-P-368 cross function in the cell integrity pathway occurs only when it is highly overproduced or when Ste5 is missing. This behavior suggests that Ste5, which has been proposed to be a tether for the kinases in the mating pathway, contributes to Ste7 specificity and fidelity of signal transmission. (C) 1995 Wiley-Liss, Inc.