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Molecular and Cellular Biology, June 2002, p. 3685-3697, Vol. 22, No. 11
0270-7306/02/$04.00+0     DOI: 10.1128/MCB.22.11.3685-3697.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

ACK Family Tyrosine Kinase Activity Is a Component of Dcdc42 Signaling during Dorsal Closure in Drosophila melanogaster

Kai Ping Sem,1 Baharak Zahedi,1 Ivan Tan,2 Maria Deak,3 Louis Lim,2,4 and Nicholas Harden1*

Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia V5A 1S6, Canada,1 Glaxo-IMCB Laboratory, Institute of Molecular and Cell Biology, Singapore 117609, Republic of Singapore,2 MRC Protein Phosphorylation Unit, Department of Biochemistry, University of Dundee, Dundee DD1 5EH,3 Department of Neurochemistry, Institute of Neurology, London WC1 1PJ, United Kingdom4

Received 24 August 2001/ Returned for modification 25 October 2001/ Accepted 11 March 2002

We have characterized Drosophila melanogaster ACK (DACK), one of two members of the ACK family of nonreceptor tyrosine kinases in Drosophila. The ACKs are likely effectors for the small GTPase Cdc42, but signaling by these proteins remains poorly defined. ACK family tyrosine kinase activity functions downstream of Drosophila Cdc42 during dorsal closure of the embryo, as overexpression of DACK can rescue the dorsal closure defects caused by dominant-negative Dcdc42. Similar to known participants in dorsal closure, DACK is enriched in the leading edge cells of the advancing epidermis, but it does not signal through activation of the Jun amino-terminal kinase cascade operating in these cells. Transcription of DACK is responsive to changes in Dcdc42 signaling specifically at the leading edge and in the amnioserosa, two tissues involved in dorsal closure. Unlike other members of the ACK family, DACK does not contain a conserved Cdc42-binding motif, and transcriptional regulation may be one route by which Dcdc42 can affect DACK function. Expression of wild-type and kinase-dead DACK transgenes in embryos, and in the developing wing and eye, reveals that ACK family tyrosine kinase activity is involved in a range of developmental events similar to that of Dcdc42.


* Corresponding author. Mailing address: Department of Molecular Biology and Biochemistry, Simon Fraser University, 8888 University Dr., Burnaby, BC V5A 1S6, Canada. Phone: (604) 291-5644. Fax: (604) 291-5583. E-mail: nharden{at}sfu.ca.


Molecular and Cellular Biology, June 2002, p. 3685-3697, Vol. 22, No. 11
0022-538X/02/$04.00+0     DOI: 10.1128/MCB.22.11.3685-3697.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.




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