Language
Country/Area
No result found
The breakthrough of 1979: How was the mysterious process of a new protein modification discovered?
In 1979, the scientific community encountered a breakthrough discovery, which opened a new chapter in protein phosphorylation. That summer, research on the kinase activity associated with T protein and v-Src in polyketidevirus led to the discovery of tyrosine phosphorylation. This process involves the transfer of phosphate (PO43−) to tyrosine residues in proteins, primarily through enzymes called tyrosine kinases.
Tyrosine phosphorylation is a key step in signal transduction and regulation of enzyme activity.
Following this discovery, Src became the first tyrosine kinase, leading to a rapid increase in the number of known tyrosine kinases. With the emergence of rapid DNA sequencing technology and PCR, the discovery of new tyrosine kinases and receptor tyrosine kinases has mushroomed. As of 2002, 58 of the 90 known human tyrosine kinases are receptor tyrosine kinases. At the same time, 108 protein phosphatases play the role of removing phosphate, demonstrating the antagonistic relationship between kinases and phosphatases.
The core of signal transmission
Ushiro and Cohen revealed the regulatory role of tyrosine phosphorylation in intracellular processes in 1980 and showed how it affects tyrosine kinase activity in mammalian cells. Subsequent studies showed that this change is the basis of the Ras-MAPK signaling pathway. This signaling pathway is involved in the transmission of proliferation signals. Its core steps include:
- Binding of growth factors and receptors
- Receptor dimerization and autophosphorylation
- Coupling of receptors and adapter SH2 domain proteins
- Activation of Ras and subsequent MAP kinase signaling into the genome
This conduction process triggers signal transduction from genes to products, affecting cell growth and reproduction.
Tyrosine kinase categories and functions
Tyrosine kinases can be divided into two main categories: receptor tyrosine kinases and non-receptor tyrosine kinases. Receptor tyrosine kinases have an N-terminal extracellular binding domain that can bind to activating ligands; non-receptor tyrosine kinases are mainly intracellular soluble proteins that are bound to membranes through some post-permeable transcriptional modifications.
Protein tyrosine kinase catalyzes the transfer of gamma-phosphate from ATP to tyrosine residues, while protein tyrosine phosphatase is responsible for the removal of phosphate. This dynamic balance of release and reintroduction of phosphate groups is critical to cell growth, differentiation, and metabolic processes.
Multiple roles of tyrosine phosphorylation
In cell growth factor signaling, tyrosine phosphorylation of certain target proteins is required, which promotes their enzymatic activity. Under the stimulation of growth factors such as EGF, PDGF or FGF, the corresponding SH2 domain can bind to specific phosphotyrosine, thereby promoting the activation of phospholipase C.
The early signal of tyrosine phosphorylation can effectively regulate cell proliferation, migration and adhesion.
In addition, tyrosine phosphorylation also plays an important role in cell shape, adhesion and movement. For example, p140Cap protein is rapidly phosphorylated within 15 minutes after cells adhere to integrin ligands. This rapid response demonstrates the central role of tyrosine phosphorylation in the regulation of cell behavior.
Association with disease
Changes in tyrosine kinase activity are closely related to many diseases, including cancer, diabetes, and pathogenic infections. Understanding the CD4-mediated negative signaling mechanism is of great significance for studying the gradual depletion of CD4+ T lymphocytes caused by HIV. With HIV infection, in activated B-cell-like diffuse large B-cell lymphoma (DLBCL), JAK1 activates IL-6 and IL-10 cytokines through non-classical epigenetic regulatory mechanisms, showing that tyrosine kinases play a role in important role in the disease process.
Looking to the future
The discovery and understanding of tyrosine phosphorylation not only reveals basic biological processes in life activities, but also opens up new possibilities in medical research and treatment. As technology advances, our understanding of this process will continue to deepen, perhaps leading us to find solutions to more diseases. So, in future scientific exploration, can we unlock more mysteries of life and make greater contributions to human health?
