Drosophila ASPP regulates C-terminal Src kinase activity

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

SN - 1534-5807

VL - 13

SP - 773

EP - 782

JO - Developmental Cell

JF - Developmental Cell

IS - 6

ER -