Physiology, Growth Factor

Excerpt

A growth factor, as initially defined, is a secreted biologically active molecule that can affect the growth of cells. This definition has become expanded to include secreted molecules that promote or inhibit mitosis or affect cellular differentiation. Growth factors can act on specific cell surface receptors that subsequently transmit their growth signals to other intracellular components and eventually result in altered gene expression. The general process of transmitting an external molecular signal to a cell to evoke a cellular response is called signal transduction.

Protein phosphorylation cascades play a key role in transmitting growth signals. Enzymes with kinase activity or phosphatase activity are important in this signaling process. Kinases put a phosphate group on a protein, and phosphatases take off a phosphate group. Many growth factors are peptides/proteins, and this type of growth factor typically binds with a high affinity to a specific surface receptor, which is a plasma membrane-bound protein. A peptide is defined as having between two and 50 amino acid residues, whereas a protein has more than 50 amino acid residues. The receptor-binding site for peptide/protein growth factors is on the outer cell membrane surface, in other words, the extracellular domain. Most cell surface receptors for growth factors show tyrosine kinase activity, meaning they put a phosphate group on a downstream protein tyrosine residue. An exception is the surface receptors for the transforming growth factor-beta (TGF-beta) family of cytokines. When activated by the binding of TGF-beta cytokines, this receptor can phosphorylate downstream proteins on serine and threonine residues. "Downstream" here means an event triggered after TGF-beta binding to its receptor.

Some growth factors are small peptides called cytokines. While all cytokines affect signal transduction pathways, only those cytokines affecting cell growth/differentiation signaling pathways are considered growth factors. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is an example of a cytokine growth factor since it promotes the production of white blood cells by stem cells. Examples of protein growth factors are vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), and platelet-derived growth factor (PDGF). Growth factor specificity to particular cell types is achievable by the expression of highly specific cell surface receptors. For example, some growth factors act only on hematopoietic cells, which are cells derived from bone marrow.

Some growth factors like lipid-soluble steroid hormones, do not have a surface receptor and can directly pass through the cell's plasma membrane, bind to an intracellular protein receptor, or nuclear receptors, and then transmit a growth signal. Glands produce all hormones and secrete them into the circulatory system. Estrogens, androgens, and progestogens are examples of steroid hormones that are growth factors. Not all hormones are growth factors, only those affecting cell growth/differentiation. Even simple small molecules such as nitric oxide or reactive oxygen species (ROS) can act as growth factors.