Drosophila ASPP regulates C-terminal Src kinase activity.
Src-family kinases (SFKs) control a variety of biological processes, from cell proliferation and differentiation to cytoskeletal rearrangements. Abnormal activation of SFKs has been implicated in a wide variety of cancers and is associated with metastatic behavior (Yeatman, 2004). SFKs are maintained in an inactive state by inhibitory phosphorylation of their C-terminal region by C-terminal Src kinase (Csk). We have identified Drosophila Ankyrin-repeat, SH3-domain, and Proline-rich-region containing Protein (dASPP) as a regulator of Drosophila Csk (dCsk) activity. dASPP is the homolog of the mammalian ASPP proteins, which are known to bind to and stimulate the proapoptotic function of p53. We show that dASPP is a positive regulator of dCsk. First, dASPP loss-of-function strongly enhances the specific phenotypes of dCsk mutants in wing epithelial cells. Second, dASPP interacts physically with dCsk to potentiate the inhibitory phosphorylation of Drosophila Src (dSrc). Our results suggest a role for dASPP in maintaining epithelial integrity through dCsk regulation.
Apoptosis and Proliferation Control Laboratory, Cancer Research UK, London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3PX, United Kingdom.
Paul F
PF
Langton
Julien
J
Colombani
Birgit L
BL
Aerne
Nicolas
N
Tapon
D000818:Animals; D030801:Animals, Genetically Modified; D017487:Ankyrins / Q000737:chemistry; D015153:Blotting, Western; D000081247:CSK Tyrosine-Protein Kinase; D029721:Drosophila Proteins / Q000502:physiology*; D004331:Drosophila melanogaster; D004847:Epithelial Cells / Q000378:metabolism; D047468:Immunoprecipitation; D010641:Phenotype; D010766:Phosphorylation; D011392:Proline / Q000737:chemistry; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D015398:Signal Transduction; D018909:src Homology Domains; D019061:src-Family Kinases
D017487:Ankyrins; D029721:Drosophila Proteins; D011392:Proline; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; C000609101:Csk protein, Drosophila; D019061:src-Family Kinases