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The key to cell growth: Why is Ras protein a switch in the MAPK/ERK pathway?
The process of cell growth is a complex and exquisite mechanism, in which the MAPK/ERK pathway (also known as the Ras-Raf-MEK-ERK pathway) is an important message channel that transmits signals from the cell surface to the nucleus. When external signaling molecules bind to receptors on the cell surface, this chain of message transmission begins. The ultimate purpose of the signal is to change the expression of DNA and promote cellular changes, such as cell division.
"The MAPK/ERK pathway plays a key role in almost all cellular activities, especially during cell proliferation and differentiation."
The core of the MAPK pathway lies in its member Ras protein, a small GTPase. When the signaling molecule binds to the receptor, the Ras protein is activated by exchanging GTP molecules with GDP molecules. In the subsequent reaction, Ras activates RAF kinase, which further activates other protein kinases, forming a kinase cascade that ultimately triggers the activation of transcription factors in the cell.
Activation process of Ras
In the MAPK/ERK pathway, receptor tyrosine kinases (such as epidermal growth factor receptor EGFR) are activated by external ligands (such as epidermal growth factor EGF). EGF binds to EGFR, resulting in phosphorylation of the receptor's tyrosine residues. Subsequently, docking proteins such as GRB2 bind to the phosphorylated portion of the receptor through its SH2 domain and associate with the SOS protein that promotes nucleotide exchange. This process activates Ras and converts it into an active state.
"Ras protein plays an important switch role in cell signaling, directly affecting multiple downstream signaling pathways."
Kase cascade reaction
When Ras is activated, it further activates RAF kinase. Activation of this kinase leads to the phosphorylation of MAPK/ERK kinase (MEK), which in turn activates MAPK. These MAPKs were originally called extracellular signal-regulated kinases (ERKs). Their multiple phosphorylation targets ultimately affect protein translation and expression when cells receive growth factor signals, thereby regulating cell growth and division.
Regulation of cell cycle
The MAPK pathway also plays a crucial role in cell cycle entry and proliferation. When growth factors such as EGF are present, they trigger the activation of EGFR and initiate the transduction of a series of external signals. These signals ultimately lead to sustained activation of ERK, a process critical for cell cycle progression.
"Because ERK activity is directly linked to cell cycle progression, abnormal signal transduction often leads to tumor formation."
Clinical significance
In many cancers, such as melanoma, defects in the MAPK/ERK pathway lead to uncontrolled cell growth. This has prompted scientists to research and develop drugs that can interfere with this pathway, such as RAF kinase inhibitors and MEK inhibitors. These therapies have shown potential in treating certain types of cancer and have also spurred in-depth research on Ras proteins and related pathways.
Obviously, the MAPK/ERK pathway plays a pivotal role in cell growth and carcinogenesis. It can be said to be a biological "switch." This makes us wonder whether more precise treatments will be developed in the future to regulate this pathway and bring new hope to patients suffering from cancer.
