論文 - 詳細
| RRC ID | 29022 |
|---|---|
| 著者 | Meili R, Ellsworth C, Firtel RA. |
| タイトル | A novel Akt/PKB-related kinase is essential for morphogenesis in Dictyostelium. |
| ジャーナル | Curr Biol |
| Abstract |
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 effectors 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. |
| 巻・号 | 10(12) |
| ページ | 708-17 |
| 公開日 | 2000-6-15 |
| DOI | 10.1016/s0960-9822(00)00536-4 |
| PII | S0960-9822(00)00536-4 |
| PMID | 10873800 |
| MeSH | Amino Acid Sequence Animals Cloning, Molecular DNA, Complementary Dictyostelium / enzymology* Dictyostelium / growth & development* Gene Expression Regulation, Developmental Gene Expression Regulation, Enzymologic Genetic Complementation Test Molecular Sequence Data Morphogenesis Protein Serine-Threonine Kinases / chemistry Protein Serine-Threonine Kinases / genetics Protein Serine-Threonine Kinases / metabolism* Protozoan Proteins Sequence Homology, Amino Acid |
| IF | 9.601 |
| 引用数 | 65 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY |
| リソース情報 | |
| 細胞性粘菌 | S00007 |