C-elegans serine-threonine kinase KIN-29 modulates TGFβ signaling and regulates body size formation -: art. no. 8

C-elegans serine-threonine kinase KIN-29 modulates TGFβ signaling and regulates body size formation -: art. no. 8
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DOI:
10.1186/1471-213x-5-8
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发表时间:
2005-04-19
影响因子:
--
通讯作者:
Padgett, RW
Padgett, RW
中科院分区:
生物学4区
文献类型:
--
作者:
Maduzia, LL;Roberts, AF;Padgett, RW

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背景:线虫体内有两条明确定义的转化生长因子β信号通路。Sma/Mab途径影响个体大小、形态发生、雄性尾巴发育和毛刺形成,而Daf途径调节进入和退出Dauer状态。为了确定在Sma/Mab途径中调节转化生长因子β信号的其他因素,我们对小动物进行了基因筛查,并鉴定了KIN-29。结果:KIN-29编码一个含有细胞质丝氨酸-苏氨酸激酶和一个新的C末端结构域的蛋白。激酶结构域是EMK(ELKL基序激酶)家族的远亲成员,与微管相互作用。我们发现丝氨酸-苏氨酸激酶结构域具有体外活性。KIN-29突变会导致小动物,但不会像几个Sma/Mab信号转导分子那样影响雄性尾巴的形态。成虫比野生型小,但发育也更慢。KIN-29的拯救是通过在神经元或皮下组织中表达来实现的。在双突变组合中观察到与Dauer途径的相互作用,这已经在Sma/Mab途径突变中观察到。KIN-29位于Sma/Mab途径靶基因Ion-1的上游。结论:Kin-29是Sma/Mab途径的一种新的调节剂。它在神经元和皮下组织中发挥调节身体大小的功能,但不影响所有转化生长因子β的输出,如尾巴形态发生。
Background: In C. elegans there are two well- defined TGF beta- like signaling pathways. The Sma/ Mab pathway affects body size morphogenesis, male tail development and spicule formation while the Daf pathway regulates entry into and exit out of the dauer state. To identify additional factors that modulate TGF beta signaling in the Sma/ Mab pathway, we have undertaken a genetic screen for small animals and have identified kin- 29.Results: kin- 29 encodes a protein with a cytoplasmic serine- threonine kinase and a novel C-terminal domain. The kinase domain is a distantly related member of the EMK ( ELKL motif kinase) family, which interacts with microtubules. We show that the serine- threonine kinase domain has in vitro activity. kin- 29 mutations result in small animals, but do not affect male tail morphology as do several of the Sma/ Mab signal transducers. Adult worms are smaller than the wild- type, but also develop more slowly. Rescue by kin- 29 is achieved by expression in neurons or in the hypodermis. Interaction with the dauer pathway is observed in double mutant combinations, which have been seen with Sma/ Mab pathway mutants. We show that kin- 29 is epistatic to the ligand dbl- 1, and lies upstream of the Sma/ Mab pathway target gene, Ion- 1.Conclusion: kin- 29 is a new modulator of the Sma/ Mab pathway. It functions in neurons and in the hypodermis to regulate body size, but does not affect all TGF beta outputs, such as tail morphogenesis.