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The magic of cell signaling: Why receptor tyrosine kinases are a potential key to cancer.
In the field of cell biology, receptor tyrosine kinases (RTKs) are considered to be high-affinity cell surface receptors for many polypeptide growth factors, cytokines, and hormones. Of the 90 unique tyrosine kinase genes found in the human genome, 58 encode receptor tyrosine kinase proteins. These receptors play key roles in regulating normal cellular processes and also play important roles in the development and progression of many cancers.
Receptor tyrosine kinases are activated by dimerization and substrate presentation and are part of a larger family of protein tyrosine kinases that include receptor tyrosine kinase proteins with transmembrane domains and Non-receptor tyrosine kinase without a transmembrane domain. The RTKs, including the EGF and NGF receptors, were first discovered in the 1960s, but their classification was not clarified until the 1970s.Mutations in receptor tyrosine kinases trigger a series of signaling cascades with multiple effects on protein expression.
Receptor structure
Most RTKs are single subunit receptors, but some exist as multimers, such as the disulfide-linked dimer formed by the insulin receptor in the presence of hormone (insulin). Each monomer has a hydrophobic transmembrane domain consisting of 25 to 38 amino acids, an extracellular N-terminal region rich in conserved elements, and an internal C-terminal region. These domains primarily contain ligand binding sites that bind to specific growth factors or hormones.
After the activated receptor is activated in the catalytic region of its internal C-terminal region, it will undergo autophosphorylation, thereby inducing downstream signal transduction.
Signal transduction
When growth factors bind to the extracellular domain of RTK, they trigger receptor dimerization, which rapidly activates its tyrosine kinase activity in the cytoplasm. This process directs autophosphorylation on specific tyrosine residues within the receptor. Such phosphorylation changes the structure of the receptor, forming different proteins that can bind and initiate downstream signal transduction pathways, transmitting signals to the interior of the cell.
RTK activation is not only related to cell proliferation, but also involves cell survival and assists in communication between cells.
Receptor tyrosine kinase family
Receptor tyrosine kinases can be divided into several major families, including the epidermal growth factor receptor family (EGFR), the fibroblast growth factor receptor family (FGFR), and the vascular endothelial growth factor receptor family (VEGFR). These different families of RTKs regulate different biological processes and are also closely related to the progression of multiple diseases.
Epidermal growth factor receptor family
Like members of the EGFR family, these receptors play an integral role in the development of a variety of human cancers. Excessive EGFR signaling has been associated with the development of various solid tumors, further emphasizing the importance of RTKs in cancer.
Fibroblast growth factor receptor family
Members of this family have broad ligand binding properties and their activation not only promotes cell proliferation but is also involved in tissue formation and repair processes.
Therapeutic potential
Receptor tyrosine kinases have become attractive targets for drug therapy because of their importance in a variety of cellular abnormalities, such as cancer. Currently, many drugs targeting receptor tyrosine kinases have been approved, such as Herceptin antibodies targeting HER2 overexpression, which can effectively interfere with the proliferation signals of tumor cells.
This is not only a way to treat cancer, but also an in-depth exploration of cell signaling regulation.
However, despite the important role of RTKs in medicine, the research community still faces many challenges, such as drug resistance and personalized treatment for specific patient groups. How will this affect the direction of future cancer treatment and research, and will it bring more hope to human health?
