Identification of FIP200 interaction with the TSC1-TSC2 complex and its role in regulation of cell size control

Related Experiment Video

Updated: Aug 9, 2026

Aip1p Dynamics Are Altered by the R256H Mutation in Actin
08:57

Aip1p Dynamics Are Altered by the R256H Mutation in Actin

Published on: July 30, 2014

Boyi Gan1, Zara K Melkoumian, Xiaoyang Wu

  • 1Department of Molecular Medicine, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.

The Journal of Cell Biology
|July 27, 2005
PubMed

Insights

Focal adhesion kinase family interacting protein of 200 kD (FIP200) regulates cell size by interacting with the TSC1-TSC2 complex. This interaction influences S6 kinase phosphorylation, particularly under nutrient stimulation.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • FIP200 (focal adhesion kinase [FAK] family interacting protein of 200 kD) is known to bind FAK and modulate its activity.
  • The TSC1-TSC2 complex is a key regulator of cell growth and metabolism.
  • Understanding FIP200's role beyond FAK interaction is crucial for cell biology insights.

Purpose of the Study:

  • To investigate the interaction between FIP200 and the TSC1-TSC2 complex.
  • To elucidate FIP200's function in cell size regulation and S6 kinase activation.
  • To determine the specific conditions under which FIP200 influences cellular signaling.

Main Methods:

  • Co-immunoprecipitation assays to confirm protein interactions.
  • RNA interference (RNAi) to knock down endogenous FIP200.
  • Analysis of cell size and S6 kinase phosphorylation levels.
  • Stimulation assays using nutrients, energy, or serum.

Main Results:

  • FIP200 directly binds to TSC1, forming a complex with TSC1-TSC2.
  • Association with TSC1-TSC2 increases cell size and S6 kinase phosphorylation, independent of FAK.
  • Knockdown of FIP200 reduces cell size and S6 kinase phosphorylation, requiring TSC1.
  • FIP200 mediates nutrient-induced S6 kinase activation but not energy- or serum-induced activation.

Conclusions:

  • FIP200 plays a significant role in regulating cell size through its interaction with the TSC1-TSC2 complex.
  • FIP200 acts as a mediator for nutrient-sensitive signaling pathways impacting cell growth.
  • These findings reveal a novel function of FIP200 in cellular homeostasis and growth control.

More Related Videos

Vasodilation of Isolated Vessels and the Isolation of the Extracellular Matrix of Tight-skin Mice08:09

Vasodilation of Isolated Vessels and the Isolation of the Extracellular Matrix of Tight-skin Mice

Published on: March 24, 2017

Simultaneous Visualization of the Dynamics of Crosslinked and Single Microtubules In Vitro by TIRF Microscopy07:20

Simultaneous Visualization of the Dynamics of Crosslinked and Single Microtubules In Vitro by TIRF Microscopy

Published on: February 18, 2022

Related Concept Videos

Phosphoinositides and PIPs01:42

Phosphoinositides and PIPs

Phosphoinositides are a group of phospholipids containing a glycerol backbone with two fatty acid chains and a phosphate attached to a myoinositol sugar ring. The inositol head group extends into the cytoplasm, where it is modified by adding phosphate groups to form phosphatidylinositol phosphates or PIPs.
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
Cells Coordinate Growth and Proliferation02:36

Cells Coordinate Growth and Proliferation

Cell size is a significant factor impacting cellular design, function, and fitness. There exists some internal coordination by which cells double their masses before division, thus, achieving homeostasis. Coordination between cell growth and proliferation depends on the checkpoints in between cell cycle phases. Loss of coordination or failure in the checkpoint mechanism can drive the cell to uncontrolled growth and loss of cellular function. Like dividing cells that coordinate cellular growth,...
The Cell Cycle Control System01:28

The Cell Cycle Control System

The cell cycle regulation directs how a cell proceeds from one phase to the next and begins mitosis. The cell cycle control system includes intracellular regulatory molecules and external triggers. They provide "stop" or "advance" signals and operate at specific cell cycle stages termed checkpoints to ensure that a particular process is completed before the cell advances to the next phase.
Cyclins and cyclin-dependent kinases (Cdks) are the primary cell cycle regulators and function at the cell...
Molecular Factors Affecting Cell Division01:27

Molecular Factors Affecting Cell Division

Several external and internal factors influence the initiation and inhibition of cell division. For instance, the death of nearby cells or the release of human growth hormone (hGH) promotes cell division. In contrast, lack of hGH or crowding of cells can inhibit cell division.
Several proteins function as internal regulators to ensure each cell cycle stage is completed faithfully before proceeding to the next. Regulator molecules may act directly or influence the activity or production of other...