Drosophila ASPP regulates C-terminal Src kinase activity.
Paul F Langton1, Julien Colombani, Birgit L Aerne
1Apoptosis and Proliferation Control Laboratory, Cancer Research UK, London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3PX, United Kingdom.
Developmental Cell
|December 7, 2007
Summary
Drosophila ASPP (dASPP) protein regulates Drosophila Csk (dCsk) kinase activity, promoting epithelial integrity. Loss of dASPP enhances dCsk mutant phenotypes, suggesting dASPP is crucial for maintaining cell structure.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Src-family kinases (SFKs) are vital for cellular processes and implicated in cancer metastasis.
- C-terminal Src kinase (Csk) inactivates SFKs via inhibitory phosphorylation.
- Mammalian ASPP proteins regulate p53's proapoptotic function.
Purpose of the Study:
- To identify regulators of Drosophila Csk (dCsk) activity.
- To investigate the role of Drosophila ASPP (dASPP) in dCsk regulation.
- To understand dASPP's contribution to epithelial integrity.
Main Methods:
- Genetic analysis of dASPP loss-of-function mutants in Drosophila.
- Biochemical assays to study protein-protein interactions.
- Examination of dCsk and Drosophila Src (dSrc) phosphorylation states.
Main Results:
- dASPP loss-of-function exacerbates dCsk mutant phenotypes in wing epithelial cells.
- dASPP physically interacts with dCsk.
- dASPP potentiates the inhibitory phosphorylation of dSrc by dCsk.
Conclusions:
- dASPP acts as a positive regulator of dCsk activity.
- dASPP is involved in maintaining epithelial integrity through dCsk pathway modulation.
More Related Videos
Related Concept Videos
01:20The JAK-STAT Signaling Pathway
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
01:22PI3K/mTOR/AKT Signaling Pathway
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a rapamycin-insensitive companion...
01:07MAPK Signaling Cascades
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...