Drosophila Dok is required for embryonic dorsal closure
Author:
Biswas Romi1, Stein David2, Stanley E. Richard1
Affiliation:
1. Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA. 2. Section of Molecular Cell and Developmental Biology and Institute for Cellular and Molecular Biology, University of Texas, Austin, TX 78712, USA.
Abstract
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, Ddok tyrosine phosphorylation is Src dependent; Shark associates with Ddok and Ddok localizes at the cell cortex, together with a portion of the Shark protein. The embryonic expression pattern of Ddok resembles the expression pattern of Shark. Ddok loss-of-function mutant (DdokPG155)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, Ddok 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 Ddok is expected to provide novel insights into the function of the Dok adapter proteins.
Publisher
The Company of Biologists
Subject
Developmental Biology,Molecular Biology
Reference68 articles.
1. Agnes, F., Suzanne, M. and Noselli, S. (1999). The Drosophila JNK pathway controls the morphogenesis of imaginal discs during metamorphosis. Development126,5453-5462. 2. Bourbon, H., Gonzy-Treboul, G., Peronnet, F., Alin, M. F.,Ardourel, C., Benassayag, C., Cribbs, D., Deutsch, J., Ferrer, P., Haenlin, M. et al. (2002). A P-insertion screen identifying novel X-linked essential genes in Drosophila. Mech. Dev.110, 71-83. 3. Bradshaw, J. M. and Waksman, G. (2002). Molecular recognition by SH2 domains. Adv. Protein Chem.61,161-210. 4. Carpino, N., Wisniewski, D., Strife, A., Marshak, D., Kobayashi,R., Stillman, B. and Clarkson, B. (1997). p62(dok): a constitutively tyrosine-phosphorylated, GAP-associated protein in chronic myelogenous leukemia progenitor cells. Cell88,197-204. 5. Chan, A. C., van Oers, N. S., Tran, A., Turka, L., Law, C. L.,Ryan, J. C., Clark, E. A. and Weiss, A. (1994). Differential expression of ZAP-70 and Syk protein tyrosine kinases, and the role of this family of protein tyrosine kinases in TCR signaling. J. Immunol.152,4758-4766.
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