A novel Akt/PKB-related kinase is essential for morphogenesis in Dictyostelium
A novel Akt/PKB-related kinase is essential for morphogenesis in Dictyostelium
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DOI：
10.1016/s0960-9822(00)00536-4
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发表时间：
2000-06-15
期刊：
影响因子：
9.2
通讯作者：
Firtel, RA
中科院分区：
文献类型：
--
作者：
Meili, R;Ellsworth, C;Firtel, RA
背景：网骨藻Akt/PKB与哺乳动物Akt/PKB同源，在早期发育过程中是细胞极性和适当趋化性所必需的。Akt/PKB激酶的激酶活性响应于中性粒细胞和网骨藻中的化学引诱物而被化学引诱物cAMP激活，所述化学引诱物cAMP经由涉及异源三聚体G蛋白和PI 3-激酶的途径起作用。结果：PKBR-1具有与Akt/PKB结构相关的激酶和羧基端结构域，但不具有PH结构域。相反，它有一个氨基末端豆蔻酰化位点，这是其组成性膜定位所必需的。与Akt/PKB一样，PKBR-1通过G蛋白依赖性途径被cAMP激活，但不需要PI 3激酶，这可能是因为PKBR-1的组成性膜定位。这得到了证明PKBR-1的激活和体内功能需要膜结合的实验的支持。PKBR-1蛋白存在于整个早期发育的所有细胞中，但随后仅限于发育聚集体中的顶端细胞，其被认为控制形态发生。PKBR-1缺失细胞在丘状阶段阻止发育，并且在形态发生和多细胞发育中有缺陷。这些表型由Akt/PKB补充，表明PKBR-1和Akt/PKB之间的功能重叠。Akt/PKB PKBR-1双基因敲除细胞表现出生长缺陷，并表现出更强的趋化性和细胞极性缺陷比Akt/PKB null cells.Conclusions：我们的研究结果扩展了以前已知的功能Akt/PKB家族成员在细胞运动和形态发生在Dictyosteoporphic多细胞发育。结果表明，Akt/PKB和PKBR-1具有重叠的效应器和生物学功能：Akt/PKB功能主要在聚集过程中控制细胞极性和趋化性，而PKBR-1是多细胞发育过程中形态发生所必需的。(C)2000爱思唯尔科技有限公司版权所有。
Background: Dictyostelium Akt/PKB is homologous to mammalian Akt/PKB and is required for cell polarity and proper chemotaxis during early development. The kinase activity of Akt/PKB kinase is activated in response to chemoattractants in neutrophils and in Dictyostelium by the chemoattractant cAMP functioning via a pathway involving a heterotrimeric G protein and PI3-kinase. Dictyostelium contains several kinases structurally related to Akt/PKB, one of which, PKBR-1, is investigated here for its role in cell polarity, movement and cellular morphogenesis during development.Results: PKBR-1 has a kinase and a carboxy-terminal domain related to those of Akt/PKB, but no PH domain. Instead, it has an amino-terminal myristoylation site, which is required for its constitutive membrane localization. Like Akt/PKB, PKBR-1 is activated by cAMP through a G-protein-dependent pathway, but does not require PI3-kinase, probably because of the constitutive membrane localization of PKBR-1. This is supported by experiments demonstrating the requirement for membrane association for activation and in vivo function of PKBR-1. PKBR-1 protein is found in all cells throughout early development but is then restricted to the apical cells in developing aggregates, which are thought to control morphogenesis. PKBR-1 null cells arrest development at the mound stage and are defective in morphogenesis and multicellular development. These phenotypes are complemented by Akt/PKB, suggesting functional overlap between PKBR-1 and Akt/PKB. Akt/PKB PKBR-1 double knockout cells exhibit growth defects and show stronger chemotaxis and cell-polarity defects than Akt/PKB null cells.Conclusions: Our results expand the previously known functions of Akt/PKB family members in cell movement and morphogenesis during Dictyostelium multicellular development. The results suggest that Akt/PKB and PKBR-1 have overlapping effecters and biological function: Akt/PKB functions predominantly during aggregation to control cell polarity and chemotaxis, whereas PKBR-1 is required for morphogenesis during multicellular development. (C) 2000 Elsevier Science Ltd. All rights reserved.