peptides or proteins. Insulin, neurotransmitters, and certain growth factors are considered these types of ligands. Some amino acids are considered these types of ligands.
SIGNALING PROCESSES With intracellular ligands, there is no ongoing signaling because the ligand binds directly to the gene and activates it. When the receptor attaches to the cell membrane, a signaling process needs to happen to send the signal into the cell. There are several intracellular signal transduction pathways that connect the ligand-receptor complex to the interior cell signal. It all starts with the ligand binding to the cell-surface receptor, which has an intracellular domain that changes its configuration in certain ways. Another signaling molecule can become activated as a result of the ligand binding. The reaction goes from upstream to downstream. The ligand itself is the most upstream and the reaction proceeds more downstream. There is amplification of the signal so that one ligand can activate many molecules downstream of it. One thing that can happen is that a protein can by phosphorylated in order to cause it to be activated. This is the addition of a phosphate group to a protein, which can only happen to three amino acids: threonine, serine, and tyrosine. It takes a kinase enzyme in order to cause this phosphorylation to happen. Phosphorylation can either activate, inactivate, or cause the breakdown of a protein molecule. Phosphorylation is not a permanent thing because phosphatases can ultimately remove the phosphate group. Kinases require ATP energy to do their job but the same isn’t true of a phosphatase. Growth factor signaling is an example of the phosphorylation pathway. One example of this is epidermal growth factor. It involves a series of kinases that phosphorylate different proteins. Epidermal growth factor has two receptors next to one another. These receptors act as kinases to each other’s intracellular tails. RAF is a kinase in this system that activates MEK, which in turn phosphorylates and activates ERK proteins. The ERK proteins activate many different target molecules. This three-tiered pathway is called the MAPK pathway, which stands for mitogen170
