Receptor-dependent and tyrosine phosphatase-mediated inhibition of GSK3 regulates cell fate choice

被引：47

作者：

Kim, L

Harwood, A

Kimmel, AR

机构：

[1] NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA

[2] UCL, Dept Biol, London WC1E 6BT, England

[3] UCL, MRC, Mol Cell Biol Lab, London WC1E 6BT, England

来源：

DEVELOPMENTAL CELL | 2002年 / 3卷 / 04期

基金：

英国惠康基金;

关键词：

D O I：

10.1016/S1534-5807(02)00269-1

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Asymmetric body axis formation is central to metazoan development. Dictyostelium establishes an anterior/posterior axis utilizing seven-transmembrane cAMP morphogen receptors (CARs) and GSK3-mediated signal transductions that has a parallel with metazoan Wnt/Frizzled-GSK3 pathways. In Dictyostelium, GSK3 promotes posterior cell patterning but inhibits anterior cell differentiation. Tyrosine kinase ZAK1 mediates GSK3 activation. We now show that CAR4 regulates a tyrosine phosphatase that inhibits GSK3 activity. We have also identified essential phosphotyrosines in GSK3, confirmed their role in activated/deactivated regulation and cell fate decisions, and relate them to the predicted 3D structure of GSK3beta. CARs differentially regulate GSK3 activity by selectively activating a tyrosine phosphatase or kinase for pattern formation. The findings may provide a comparative understanding of CAR-GSK3 and Wnt/Frizzled-GSK3 pathways.

引用

页码：523 / 532

页数：10

共 34 条

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