Growth Factor Families
TGFs and Receptors are a diverse group of growth factors and their associated receptors involved in regulating various cellular processes such as cell growth, differentiation, and immune modulation.TGF-β Superfamily
Classification of Growth Factors and Receptors
A growth factor is a compound that is secreted by cells and acts outside the cell to promote cell proliferation, differentiation, and growth. Based on different growth factor signaling pathways, growth factors and receptors can be categorized into three groups.
The first group consists of tyrosine kinase receptors. These receptors, such as the epidermal growth factor receptor (EGFR) and hepatocyte growth factor receptor (HGFR), are monokinase in nature. They catalyze the autophosphorylation of receptor tyrosine residues in molecules like epidermal growth factor (EGF) and hepatocyte growth factor (HGF). This phosphorylation serves as the starting point for the cell's secondary signaling pathway.
The second group comprises intracellular tyrosine kinase receptors. These receptors are typically phosphorylated by translated tyrosine kinase factors, which then activate signaling pathways. Examples of intracellular tyrosine kinase receptors include Janus kinase, rII interferon receptor, and insulin receptor, among others.
The third category encompasses guanylate acylase receptors. These receptors are activated by the G protein found in the cell membrane. They transmit signals from within the cell to the active center of the enzyme, triggering various cellular responses.
Molecular Mechanism of Growth Factors and Receptors
1. Role of Growth Factors
Growth factors initiate a series of cell signaling processes by binding to receptors on the cell surface. This process can be divided into three steps:
a. Receptor activation: The growth factor binds to the receptor's binding site, leading to receptor activation and subsequent receptor-specific phosphorylation.
b. Signal transduction: Phosphorylated receptors bind to various polymers, facilitating the entry of signal molecules into the cytoplasm. These molecules interact to form complex signaling pathways.
c. Cellular response: The signal is transmitted to the nucleus through the transduction pathway, regulating the transcription and translation of cellular genes. This process generates the physiological response of the cell.
2. Classification of Receptors
Cell surface receptors can be classified into two categories: cell membrane receptors and intracellular receptors.
Cell membrane receptors directly interact with the extracellular matrix, resulting in highly efficient signal transmission. Intracellular receptors, on the other hand, are typically mediated by cell membrane receptors. They regulate the expression of cellular genes through various pathways, triggering a series of cellular responses.
3. Modulation of Growth Factor Signaling Pathways
The signaling pathways of growth factors are complex and tightly regulated within the appropriate cellular environment. This regulation involves not only the actions of growth factors and receptors but also a multitude of signal transduction proteins. These proteins include signal transducers, regulators, substrate enzymes, and others.
The regulation of signaling pathways plays a crucial role in various biological processes. For instance, in humans, growth factors like EGF and IGF play a critical role in regulating the insulin-like growth factor (IGF)-1R signaling pathway. Deficiency in IGF-1R results in the downregulation of angiogenic growth factors, tyrosine kinases, tumor necrosis factor-α (TNF-α), and tumor necrosis factor-β (TNF-β) expression levels, thereby reducing the ability of the extracellular matrix to maintain stability.
Molecular Mechanism of Growth Factors and Receptors: A Summary
In summary, the molecular mechanism of growth factors and receptors involves a complex interplay of multiple levels and pathways. By delving into the interaction and signal transduction mechanisms between growth factors and receptors, we can enhance our comprehension of cell signal transduction and lay a stronger theoretical foundation for the design and discovery of novel biopharmaceuticals.