8: (T3) Signal Transduction

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Metazoan organisms are not just conglomerations of cells that happen to stick together. The cells each have specific functions that must be coordinated with one another in order to assure the survival of the organism and thus the shared survival of the component cells. If coordination is required, then a method of communication between cells is also required. In fact, it is even more complicated than that because the communications between the cells only scratches the surface and the intracellular communication that goes on to coordinate multiple cellular activities in response to an external signal is usually far more complex than the initial transmission of that signal.

8.1: Introduction to Signal Transduction
There are three primary modes of intercellular communication. (1) These are direct contact between signaling molecules bound to the membranes of two adjacent cells, (2) short-range soluble signals that diffuse over short distances, and (3) long-range soluble signals that are secreted into the circulation to be carried anywhere in the body.
8.2: Receptors and Ligands
A protein that happens to bind something is not necessarily a receptor. A receptor is defined as a protein that binds to an extracellular ligand, and then undergoes a con- formational or biochemical shift in such a way that it initiates a chain of intracellular events by which the cell reacts to the extracellular signal. What are these ligands and their receptors?
8.3: 7-TM receptors (G-protein-coupled)
The 7-transmembrane receptors, or G-protein-coupled receptors are, unsurprisingly, a family of proteins that pass through the cell membrane 7 times. The amino terminal is extracellular and the carboxyl terminal is intracellular.
8.4: Receptor Tyrosine Kinases
In contrast to the 7-TM receptors, the receptor tyrosine kinases (RTK) pass through the membrane only once, and have a built-in enzyme domain - a protein tyrosine kinase. RTKs must dimerize to be functional receptors, although individual RTKs can bind to their ligands. The ligands also dimerize, and when a dimerized receptor is activated, the kinase domains cross-phosphorylate the cytoplasmic domain on the other receptor unit.
8.5: Calcium Ion Signaling
Signaling by increasing cytosolic calcium is an important and ubiquitous intracellular coordination mechanism. We already saw that release of Ca2+ in muscle cells is required to allow contraction of each sarcomere, and the positioning of the sarcoplasmic reticulum makes possible rapid changes in concentration nearly simultaneous across the entire cell. Another extremely important physiological mechanism that relies on calcium is fertilization.

Thumbnail: Simplified representation of major signal transduction pathways in mammals. (CC BY-SA 3.0; cybertory & Roadnottaken).