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Vol. 19, Issue 1, 378-393, January 2008

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Using Bcr-Abl to Examine Mechanisms by Which Abl Kinase Regulates Morphogenesis in Drosophila

Traci L. Stevens^*,, Edward M. Rogers, Laura M. Koontz^,, Donald T. Fox^,, Catarina C.F. Homem, Stephanie H. Nowotarski, Nicholas B. Artabazon^*, and Mark Peifer^,

Department of Biology and Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-3280; and *Department of Biology, Randolph-Macon College, Ashland, VA 23005

Submitted January 8, 2007; Revised October 5, 2007; Accepted October 12, 2007
Monitoring Editor: Jean Schwarzbauer

Signaling by the nonreceptor tyrosine kinase Abelson (Abl) plays key roles in normal development, whereas its inappropriate activation helps trigger the development of several forms of leukemia. Abl is best known for its roles in axon guidance, but Abl and its relatives also help regulate embryonic morphogenesis in epithelial tissues. Here, we explore the role of regulation of Abl kinase activity during development. We first compare the subcellular localization of Abl protein and of active Abl, by using a phosphospecific antibody, providing a catalog of places where Abl is activated. Next, we explore the consequences for morphogenesis of overexpressing wild-type Abl or expressing the activated form found in leukemia, Bcr-Abl. We find dose-dependent effects of elevating Abl activity on morphogenetic movements such as head involution and dorsal closure, on cell shape changes, on cell protrusive behavior, and on the organization of the actin cytoskeleton. Most of the effects of Abl activation parallel those caused by reduction in function of its target Enabled. Abl activation leads to changes in Enabled phosphorylation and localization, suggesting a mechanism of action. These data provide new insight into how regulated Abl activity helps direct normal development and into possible biological functions of Bcr-Abl.

These authors contributed equally to this work.

Address correspondence to: Mark Peifer (peifer{at}unc.edu)

Abbreviations used: Abl, Abelson; AJ, adherens junction; Arm, armadillo; CML, chronic myelogenous leukemia; CNS, central nervous system; en, engrailed; Ena, Enabled; KD, kinase-dead; Ph, Philadelphia chromosome; PNS, peripheral nervous system; PTyr, phosphotyrosine.