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Components of signal transduction pathways are similar what differs is the details (Fig 9-1)
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Receptor Activated receptor Signal Second messenger Effector
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Signals: start the whole thing They re what the target cell senses Receptors: sense the signal and are activated Sensing the signal causes a change in the structure of the receptor This structural change activates the pathway Transducers: receive the signal and then pass it on in a different form They can amplify the signal or integrate signals from multiple pathways Most components of signal transduction pathways can be considered transducers Second messengers: small molecules that are released in the cell in response to a signal They can activate many other downstream components Amplifiers: increase the strength of the signal They turn one molecule of original signal into many, many molecules of second messengers or secondary signals Integrators: allow multiple signals to converge on a single response Effectors: the final step of the signaling pathway Their activation results in the effect Sometimes signals can activate multiple pathways and have multiple effects Inhibitors: turn off signaling pathways Activating an inhibitor has the same effect as inactivating the signaling event
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Signals that enter the cell (steroids, vitamin D, thyroid hormone, and retinoids) Signals that exert their effects from outside the cell (everything else) The signal is what starts everything off Signals take a variety of forms, but for our purposes there are only two The first type are signals that go into the cell, bind to internal receptors, and exert their effects Steroid hormones, vitamin D, thyroid hormone, and retinoids are the only members of this class All of the intracellular receptors ultimately activate the transcription of regulated genes The common feature of signals that enter the cell is that they are all small lipophilic molecules that can cross the cell membrane All the other signals exert their effects by binding to an extracellular receptor and initiating a cascade of signaling events They work by activating a phosphorylation cascade and/or the release of second messengers in the cell
COMMON SIGNALS
SIGNALS THAT ENTER THE CELL
Basic Concepts in Biochemistry
SIGNALS THAT DO NOT ENTER THE CELL Insulin Glucagon Cytokines Growth factors Vasopressin
Steroids (cortisol, estrogen, testosterone) Thyroid hormone Vitamin D Retinoic acid
RECEPTORS
Receptors recognize a signal molecule and transmit the signal by activating a downstream signaling pathway The same signal often has a different effect on different cell types Cytosolic receptors are soluble, cytoplasmic proteins (signal must get inside) Transmembrane receptors span a membrane (ie, signal outside, response inside)
Receptors recognize the signal first They also transmit the information that the signal has been received down the pathway The pathway (and the receptor) is named for the signal that initiates it Receptors are very specific they re activated by only one signal (or some small variations of it) Every cell type doesn t respond to the same signal in the same way The easiest way to deal with this is to deal with it as you would deal with metabolism: keep the function of the signal in mind and the function of the tissue in mind, and it will help you sort through this Some cells may not respond to a particular signal because they don t have the receptor or they may have a different downstream response because of differences in the signaling pathway itself
SOLUBLE RECEPTORS
The signal crosses the membrane and activates gene transcription Signals for soluble receptors include steroid hormones, retinoic acid, thyroid hormone, and vitamin D
Signal Transduction Pathways
Soluble intracellular receptors include the steroid hormone receptors (estrogen, progesterone and cortisol), vitamin D receptor, thyroid hormone receptor, and retinoic acid receptor Because of their insolubility in water, these hormones are transported in the blood by specific binding proteins They dissociate from the binding protein, cross the membrane, and find their receptor Hormones that diffuse across the membrane and enter the cell bind to soluble intracellular receptors The central event for a receptor involves activation getting some new activity when the signal is present (Fig 9-2) On binding the hormone, the soluble receptors change their conformation and gain the ability to bind to specific DNA sequences in the nucleus The steroid hormone receptors are transported to the nucleus only after they bind hormone, but the retinoid receptors are in the nucleus and bind to DNA even without hormone present They are both activated to start transcription when they bind hormone
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