Related Experiment Video
Updated: Jun 18, 2026
10:27
Spatio-Temporal Manipulation of Small GTPase Activity at Subcellular Level and on Timescale of Seconds in Living Cells
Published on: March 9, 2012
Aurora-A phosphorylates, activates, and relocalizes the small GTPase RalA
Kian-Huat Lim1, Donita C Brady, David F Kashatus
1Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Molecular and Cellular Biology
|November 11, 2009
Summary
Oncogenic Ras and Aurora-A kinase cooperate to promote tumor growth by activating RalA. This activation, dependent on Aurora-A phosphorylation of RalA, drives cell transformation and tumorigenesis.
Area of Science:
- Molecular oncology
- Cell signaling pathways
- Cancer biology
Background:
- The small GTPase Ras is crucial for transmitting extracellular signals and is frequently activated in human tumors.
- Aurora-A kinase regulates mitosis and can also be aberrantly activated in various cancers.
Purpose of the Study:
- To investigate the functional interaction between oncogenic Ras and Aurora-A kinase in cancer.
- To elucidate the role of Aurora-A in Ras-mediated cell transformation and tumorigenesis.
Main Methods:
- Analysis of transformed cell growth in the presence of oncogenic Ras and Aurora-A.
- Investigation of the phosphorylation status of RalA at S194.
- Assessment of RalA activation, plasma membrane translocation, and RalBP1 activation.
Main Results:
- Aurora-A enhances transformed cell growth in conjunction with oncogenic Ras.
- Cell transformation and tumorigenesis are dependent on Aurora-A-mediated phosphorylation of RalA at S194.
- Aurora-A promotes RalA activation, plasma membrane translocation, and subsequent RalBP1 activation.
Conclusions:
- Aurora-A kinase converges on oncogenic Ras signaling pathways through the RalA protein.
- The Aurora-A/RalA axis represents a potential therapeutic target in cancers driven by Ras.
- Understanding this crosstalk is vital for developing novel anti-cancer strategies.
More Related Videos
Related Concept Videos
01:24Small GTPases - Ras and Rho
Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
Three regulatory proteins control their activity:
01:14Rab Proteins
Rab proteins constitute the largest family of monomeric GTPases, of which 70 members are present in humans. Rab proteins and their effectors regulate consecutive stages of vesicle transport such as vesicle transport, docking, and fusion to the correct recipient membrane.
Rab proteins switch between a cytosolic, GDP-bound inactive state and a membrane-anchored, GTP-bound active state. By themselves, Rabs show slow rates of GDP/GTP exchange and GTP hydrolysis. Thus, Rab proteins are considered...
Rab proteins switch between a cytosolic, GDP-bound inactive state and a membrane-anchored, GTP-bound active state. By themselves, Rabs show slow rates of GDP/GTP exchange and GTP hydrolysis. Thus, Rab proteins are considered...
01:22Activation and Inactivation of G Proteins
Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high affinity and are together...
02:14GTPases and their Regulation
Guanine nucleotide-binding proteins (G-proteins), also known as GTPases, are a superfamily of proteins that regulate many cellular processes, such as cell signaling, vesicular transport, and the regulation of cell shape and motility. Mutation or dysfunction of these proteins can lead to disease. There are around 40,000 known G-proteins that can broadly be classified into two groups ‒ small G-proteins consisting of a single domain and large multi-domain G-proteins.
Large G-proteins, also known...
Large G-proteins, also known...
02:14GTPases and their Regulation
Guanine nucleotide-binding proteins (G-proteins), also known as GTPases, are a superfamily of proteins that regulate many cellular processes, such as cell signaling, vesicular transport, and the regulation of cell shape and motility. Mutation or dysfunction of these proteins can lead to disease. There are around 40,000 known G-proteins that can broadly be classified into two groups ‒ small G-proteins consisting of a single domain and large multi-domain G-proteins.
Large G-proteins, also known...
Large G-proteins, also known...
01:25Rab Cascades
Rab GTPases act in a regulated cascade during membrane fusion, helping the lipid bilayers mix. The Rab family of proteins are active when bound to GTP, and inactive when bound to GDP. Hence, they act as guanine nucleotide-dependent molecular switches. Rab-GTP recognizes and binds to long or short-range tethering proteins to capture the target vesicle. These tethers coordinate with SNAREs on the vesicle and the target membrane to assemble the trans SNARE complex that locks the mixing bilayers.