Essential knowledge 3.D.3: Signal transduction pathways link signal reception with cellular response. September 22, 2018

Signaling begins with the recognition of a chemical messenger, a ligand, by a receptor protein. 1. Different receptors recognize different chemical messengers, which can be peptides, small chemicals or proteins, in a specific one-to-one relationship. 2. A receptor protein recognizes signal molecules, causing the receptor protein’s shape to change, which initiates transduction of the signal.

3 Examples that involve a ligand and receptor protein • G-protein linked receptors

Uses for G-Protein receptor (FYI) The visual sense: the opsins use a photoisomerization reaction to translate electromagnetic radiation into cellular signals. Rhodopsin, for example, uses the conversion of 11-cis-retinal toall-trans-retinal for this purpose The gustatory sense (taste): GPCRs in taste cells mediate release of gustducin in response to bitter and sweet tasting substances. The sense of smell: receptors of the olfactory epithelium bind odorants (olfactory receptors) and pheromones (vomeronasal receptors) Behavioral and mood regulation: receptors in the mammalian brain bind several different neurotransmitters, including serotonin, dopamine, GABA, and glutamate Regulation of immune system activity and inflammation: chemokine receptors bind ligands that mediate intercellular communication between cells of the immune system; receptors such as histamine receptors bind inflammatory mediators and engage target cell types in the inflammatory response Autonomic nervous system transmission: both the sympathetic and parasympathetic nervous systems are regulated by GPCR pathways, responsible for control of many automatic functions of the body such as blood pressure, heart rate, and digestive processes Cell density sensing: A novel GPCR role in regulating cell density sensing. Homeostasis modulation (e.g., water balance).[18] Involved in growth and metastasis of some types of tumors.[19]

Interesting Fact G-Protein Receptors are the target of 40% of all modern drugs!!

Ligand-gated ion channels Ligand-gated ion channels (LGICs) are a group of transmembrane ion channel proteins which open to allow ions such as Na+, K+,Ca2+, or Cl- to pass through the membrane in response to the binding of a chemical messenger (i.e. a ligand), such as aneurotransmitter. http://highered.mcgraw-hill.com/sites/0072507470/student_view0/chapter17/animation__membrane-bound_receptors__g_proteins__and_ca2__channels.html

Ligand gated channels are used at synapses (neurotransmitter serve as the ligand)

Receptor tyrosine kinases Receptor tyrosine kinases (RTK)s are the high-affinity cell surface receptors for many polypeptide growth factors, cytokines, and hormones a kinase is a type of enzyme that transfers phosphate groups (see below) from high-energy donor molecules, such as ATP (see below) to specific target molecules (substrates); the process is termed phosphorylation.

Receptor tyrosine kinases

Signal transduction is the process by which a signal is converted to a cellular response. 1. Signaling cascades relay signals from receptors to cell targets, often amplifying the incoming signals, with the result of appropriate responses by the cell. 2. Second messengers are often essential to the function of the cascade.

Second Messengers Second messengers are molecules that relay signals from receptors on the cell surface to target molecules inside the cell, in the cytoplasm or nucleus. They relay the signals of hormones like epinephrine and greatly amplify the strength of the signal. Secondary messengers are a component of signal transduction cascades.

Example of a secondary messenger Cyclic AMP Earl Wilbur Sutherland, Jr., discovered second messengers, for which he won the 1971 Nobel Prize in Physiology or Medicine. Sutherland saw that epinephrine would stimulate the liver to convert glycogen to glucose (sugar) in liver cells, but epinephrine alone would not convert glycogen to glucose. He found that epinephrine had to trigger a second messenger, cyclic AMP, for the liver to convert glycogen to glucose. http://highered.mcgraw-hill.com/sites/0072507470/student_view0/chapter17/animation__second_messenger__camp.html

Many signal transduction pathways include: 1. Protein modifications (an illustrative example could be how methylation changes the signaling process)

2. Phosphorylation cascades in which a series of protein kinases add a phosphate group to the next protein in the cascade sequence

More Jokes… What did the Smooth Endoplasmic Reticulum say the the Rough Endoplasmic Reticulum?