Related Experiment Video
Updated: May 11, 2026
08:05
Assaying Protein Kinase Activity with Radiolabeled ATP
Published on: May 26, 2017
Control of gp130 expression by the mitogen-activated protein kinase ERK2
N A Bonito1, J Drechsler2, S Stoecker1
1Faculty of Medicine, Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital Campus, London, UK.
Oncogene
|May 21, 2013
Summary
Extracellular signal-regulated kinase 2 (ERK2) regulates the expression of glycoprotein 130 (gp130), a key molecule in Interleukin-6 (IL-6) type cytokine signaling. This finding reveals new roles for ERK2 in cancer and inflammation.
Area of Science:
- Cellular and Molecular Biology
- Cancer Research
- Signal Transduction
Background:
- Interleukin-6 (IL)-type cytokines (IL-6, OSM, LIF) signal via receptor complexes dependent on gp130.
- gp130 is the common signal-transducing molecule linking cytokines to JAKs and STATs.
- IL-6 type cytokine signaling also involves extracellular signal-regulated kinases (ERK1 and ERK2).
Purpose of the Study:
- To investigate the role of ERK1 and ERK2 in the regulation of gp130 expression and function.
- To determine if ERK1 or ERK2 specifically controls gp130 expression.
- To explore the mechanism by which ERK2 influences gp130.
Main Methods:
- Silencing of ERK2 in human osteosarcoma U2OS cells.
- Analysis of gp130 expression in cancer cell lines (osteosarcoma, breast, prostate, lung, cervical).
- Chromatin immunoprecipitation (ChIP) to assess ERK2 binding to the GP130 promoter.
- Luciferase reporter assays and mRNA stability experiments to study transcriptional regulation.
Main Results:
- Silencing ERK2, but not ERK1, inhibited gp130 expression in U2OS cells.
- This effect was observed across multiple cancer cell types.
- ERK2 was found to bind to the GP130 promoter, indicating a role in transcriptional regulation.
- Luciferase assays and mRNA stability experiments confirmed ERK2's role in regulating GP130 gene transcription.
Conclusions:
- ERK2, distinct from ERK1, plays a crucial role in regulating gp130 expression at the transcriptional level.
- These findings identify novel, non-overlapping functions for ERK1 and ERK2.
- The regulation of gp130 by ERK2 has significant implications for understanding cancer and inflammation pathways.
Related Concept Videos
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...
02:38Mitogens and the Cell Cycle
Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
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...
01:20The 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...
02:38The Ras Gene
The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a superfamily...
Ras is a superfamily...
03:03mTOR Signaling and Cancer Progression
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...