OCT 16, 2013 03:00 PM PDT
The roles of Ack family kinases in Drosophila development
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  • Associate Professor, Department of Biological Sciences, Development and Disease, Purdue University
      Dr. Chang received a B.A. in Biochemical Sciences from Harvard College (Cambridge, MA) in 1991. He obtained his Ph.D. (1995) with Dr. Gerald Rubin in the Department of Molecular and Cell Biology at University of California, Berkeley, working on genes functioning downstream of Ras GTPase in the Sevenless receptor tyrosine kinase cascade. His post-doctoral training was with Dr. Ira Mellman in the Department of Cell Biology at Yale University School of Medicine, working on J-domain proteins in Drosophila endocytosis. Dr. Chang has been on the faculty at Purdue University since 2004, and currently holds the rank of associate professor in the Department of Biological Sciences.

    Deregulation of ACK1, a non-receptor tyrosine kinase originally identified by its ability to bind to GTP-bound Cdc42 (hence the name: activated Cdc42-associated kinase)(Manser et al., 1993), correlates with the ability of primary tumors to metastasize (Mahajan et al., 2007; Mahajan et al., 2005; van der Horst et al., 2005). To understand how specific mutations in ACK1 promote oncogenic processes, we have used Drosophila to investigate the roles of Ack family kinases during animal development. The general domain organization of Ack family genes includes a N-terminal SAM (sterile ? motif), tyrosine kinase, SH3 (Src homology 3), CRIB (Cdc42/Rac interacting binding domain), proline-rich region, and C-terminal UBA (ubiquitin-associating domain). Like mammals, Drosophila has two Ack homologs, dAck and dPR2, differing by the presence of the CRIB domain. Although dAck is more similar to ACK1 in amino acid sequence, it lacks the CRIB domain, raising the question whether dAck is a true homolog of ACK1. Using molecular genetics, we show that dAck is the functional homolog of ACK1 and its tyrosine kinase activity is essential for spermatogenesis in a cell autonomous manner. dAck forms a complex with Dock (dreadlocks, the Drosophila homolog of Nck), and its kinase activity is critical for Dock subcellular localization in differentiating male germ cells. Based on these results, we propose that dAck, via SH2-phosphotyrosine interaction, recruits Dock, which assembles multi-protein complexes with its SH3 domains to specific sites to promote sperm morphogenesis.

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