title: Activated Cdc42 kinase regulates Dock localization in male germ cells during Drosophila spermatogenesis.
abstract: Deregulation of the non-receptor tyrosine kinase ACK1 (Activated Cdc42-associated kinase) correlates with poor prognosis in cancers and has been implicated in promoting metastasis. To further understand its in vivo function, we have characterized the developmental defects of a null mutation in Drosophila Ack, which bears a high degree of sequence similarity to mammalian ACK1 but lacks a CRIB domain. We show that Ack, while not essential for viability, is critical for sperm formation. This function depends on Ack tyrosine kinase activity and is required cell autonomously in differentiating male germ cells at or after the spermatocyte stage. Ack associates predominantly with endocytic clathrin sites in spermatocytes, but disruption of Ack function has no apparent effect on clathrin localization and receptor-mediated internalization of Boss (Bride of sevenless) protein in eye discs. Instead, Ack is required for the subcellular distribution of Dock (dreadlocks), the Drosophila homolog of the SH2- and SH3-containing adaptor protein Nck. Moreover, Dock forms a complex with Ack, and the localization of Dock in male germ cells depends on its SH2 domain. Together, our results suggest that Ack-dependent tyrosine phosphorylation recruits Dock to promote sperm differentiation.
authors.affiliation: Department of Biological Sciences, Purdue University, 915 West State Street, West Lafayette, IN 47907-2054, USA.
authors.forename: Abbas M
authors.initials: AM
authors.lastname: Abdallah
authors.forename: Xin
authors.initials: X
authors.lastname: Zhou
authors.forename: Christine
authors.initials: C
authors.lastname: Kim
authors.forename: Kushani K
authors.initials: KK
authors.lastname: Shah
authors.forename: Christopher
authors.initials: C
authors.lastname: Hogden
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Schoenherr
authors.forename: James C
authors.initials: JC
authors.lastname: Clemens
authors.forename: Henry C
authors.initials: HC
authors.lastname: Chang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D030801:Animals, Genetically Modified; D015153:Blotting, Western; D002454:Cell Differentiation / Q000235:genetics; D002966:Clathrin / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism*; D004705:Endocytosis; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D008856:Microscopy, Fluorescence; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D018000:Receptors, Peptide / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013090:Spermatocytes / Q000166:cytology / Q000378:metabolism*; D013091:Spermatogenesis; D018909:src Homology Domains / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002966:Clathrin; D029721:Drosophila Proteins; D005136:Eye Proteins; D008164:Luminescent Proteins; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D018000:Receptors, Peptide; C072141:boss protein, Drosophila; C099753:dock protein, Drosophila; C498593:Ack protein, Drosophila; D011505:Protein-Tyrosine Kinases