期刊
DEVELOPMENT
卷 133, 期 2, 页码 217-227出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/dev.02198
关键词
Drosophila embryogenesis; morphogenesis; shark tyrosine kinase; dorsal closure; Dok; jun kinase
资金
- NCI NIH HHS [CA26504] Funding Source: Medline
- NIGMS NIH HHS [GM 55293, GM 52761] Funding Source: Medline
- NATIONAL CANCER INSTITUTE [R01CA026504, R37CA026504] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM052761] Funding Source: NIH RePORTER
Embryonic dorsal closure (DC) in Drosophila is a series of morphogenetic movements involving the bilateral dorsal movement of the epidermis (cell stretching) and dorsal suturing of the leading edge (LE) cells to enclose the viscera. The Syk family tyrosine kinase Shark plays a crucial role in this Jun amino-terminal kinase (JNK)-dependent process, where it acts upstream of JNK in LE cells. Using a yeast two-hybrid screen, the unique Drosophila homolog of the downstream of kinase (Dok) family, Ddok, was identified by its ability to bind Shark SH2 domains in a tyrosine phosphorylation-dependent fashion. In cultured S2 embryonic cells, Dclok tyrosine phosphorylation is Src dependent; Shark associates with Dclok and Dclok localizes at the cell cortex, together with a portion of the Shark protein. The embryonic expression pattern of Dclok resembles the expression pattern of Shark. Ddok loss-of-function mutant (Ddok(PG155)) germ-line clones possess DC defects, including the loss of JNK-dependent expression of dpp mRNA in LE cells, and decreased epidermal F-actin staining and LE actin cable formation. Epistatic analysis indicates that Ddok functions upstream of shark to activate JNK signaling during DC. Consistent with these observations, Dclok mutant embryos exhibit decreased levels of tyrosine phosphorylated Shark at the cell periphery of LE and epidermal cells. As there are six mammalian Dok family members that exhibit some functional redundancy, analysis of the regulation of DC by Dclok is expected to provide novel insights into the function of the Dok adapter proteins.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据