Related Experiment Video
Updated: Nov 3, 2025
10:43
Methods to Study Mrp4-containing Macromolecular Complexes in the Regulation of Fibroblast Migration
Published on: May 19, 2016
6.9K
RAB7A Regulates Vimentin Phosphorylation through AKT and PAK
Roberta Romano1, Matteo Calcagnile1, Azzurra Margiotta1
1Department of Biological and Environmental Sciences and Technologies (DiSTeBA), University of Salento, 73100 Lecce, Italy.
Cancers
|June 2, 2021
Summary
The small GTPase RAB7A influences cell migration by regulating kinases AKT and PAK1, impacting downstream effectors like beta-catenin and MMP2, suggesting a role in cancer progression.
Area of Science:
- Cell Biology
- Molecular Biology
Background:
- RAB7A, a small GTPase, is known to regulate the late endocytic pathway.
- RAB7A also influences cell migration via RAC1 and vimentin, controlling vimentin phosphorylation and assembly.
Purpose of the Study:
- To investigate the interaction domains between RAB7A and vimentin.
- To determine if RAB7A modulates the activity of kinases involved in vimentin phosphorylation.
- To explore the downstream effects of RAB7A-mediated kinase regulation on cellular processes.
Main Methods:
- Identification of vimentin domains interacting with RAB7A.
- Assessing the impact of RAB7A expression modulation on kinase activity (AKT, PAK1).
- Quantifying phosphorylation changes at specific vimentin sites (e.g., Serine 38).
- Measuring expression levels of downstream effectors (beta-catenin, caspase 9, cofilin-1) and enzyme activity (MMP2).
Main Results:
- RAB7A regulates the activity of AKT and PAK1 kinases.
- RAB7A overexpression increases vimentin phosphorylation at Serine 38, mediated by AKT.
- RAB7A modulation affects beta-catenin and caspase 9 expression, cofilin-1 levels, and MMP2 activity.
Conclusions:
- RAB7A acts as a regulator of AKT and PAK1 kinases.
- RAB7A influences key cellular processes through these kinases and their downstream effectors.
- These findings suggest a potential role for RAB7A in various cancer hallmarks.
Related Concept Videos
01:22PI3K/mTOR/AKT Signaling Pathway
4.3K
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...
4.3K
01:20The JAK-STAT Signaling Pathway
9.8K
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...
9.8K
01:07MAPK Signaling Cascades
6.8K
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...
6.8K
03:03mTOR Signaling and Cancer Progression
4.0K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
4.0K
02:04Covalently Linked Protein Regulators
8.1K
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....
These groups modify specific amino acids in a protein....
8.1K
01:24Regulation of Angiogenesis and Blood Supply
3.0K
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
3.0K