Drosophila ASPP regulates C-terminal Src kinase activity
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Drosophila ASPP regulates C-terminal Src kinase activity. / Langton, Paul F; Colombani, Julien; Aerne, Birgit L; Tapon, Nicolas.
In: Developmental Cell, Vol. 13, No. 6, 12.2007, p. 773-82.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Drosophila ASPP regulates C-terminal Src kinase activity
AU - Langton, Paul F
AU - Colombani, Julien
AU - Aerne, Birgit L
AU - Tapon, Nicolas
PY - 2007/12
Y1 - 2007/12
N2 - 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.
AB - 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.
KW - Animals
KW - Animals, Genetically Modified
KW - Ankyrins/chemistry
KW - Blotting, Western
KW - Drosophila Proteins/physiology
KW - Drosophila melanogaster
KW - Epithelial Cells/metabolism
KW - Immunoprecipitation
KW - Phenotype
KW - Phosphorylation
KW - Proline/chemistry
KW - Protein-Tyrosine Kinases/metabolism
KW - Signal Transduction
KW - src Homology Domains
KW - src-Family Kinases
U2 - 10.1016/j.devcel.2007.11.005
DO - 10.1016/j.devcel.2007.11.005
M3 - Journal article
C2 - 18061561
VL - 13
SP - 773
EP - 782
JO - Developmental Cell
JF - Developmental Cell
SN - 1534-5807
IS - 6
ER -
ID: 213552557