Cell Signaling Flashcards
Autocrine signaling
Autocrine signaling involves the production and secretion of a ligand that binds to the cell that produced it. A good example of autocrine signaling is found in the immune system. An activated T lymphocyte secretes a growth factor that binds to its own receptors, promoting an immune response to a specific antigen.
Paracrine signaling
Paracrine signaling refers to the propagation of signals to nearby cells. An example of such signaling includes the release of inflammatory mediators (eg, histamine) from cells that act on nearby blood vessels. The mediators cause vasodilation to increase the delivery of immune cells to the region.
Endocrine signaling
Endocrine signaling is when molecules called hormones are released into the bloodstream to induce an action on another cell at a distant location in the body. A classic example is of the luteinizing hormone (LH) surge. LH is a gonadotropin hormone produced and secreted by the anterior pituitary that stimulates the ovary, resulting in ovulation. Because ovulation is instigated by a hormone produced at a location that is far away from the site of action of the hormone, this is an example of endocrine signaling.
If a secreted molecule acts on the same cell that releases it, what kind of cell signaling is this?
Autocrine signaling.
_______are proteins in the target cell that receive the “message” during signal transduction
Receptors are proteins in the target cell that receive the “message” during signal transduction
Ligands are
Ligands are molecules that bind to receptors and have an effect on them. Ligands can be endogenous or exogenous, and they can be an agonist or an antagonist.
____ activate a receptor through promoting an active conformation change in the receptor
Agonists
______ block activation of the receptor because they do not stimulate an active conformational change.
antagonists
Receptor-ligand actions are governed by five basic principles:
specificity, modularity, amplification, desensitization, and integration.
_______ refers to how selective a receptor is: does it differentiate between different ligands?
Specificity refers to how selective a receptor is: does it differentiate between different ligands?
_______ means that many secondary messenger molecules (more on those below) can be activated via binding of one single ligand to one receptor. So a single ligand can cause multiple downstream actions.
Amplification means that many secondary messenger molecules (more on those below) can be activated via binding of one single ligand to one receptor. So a single ligand can cause multiple downstream actions.
Desensitization
Desensitization is the phenomenon where receptors reduce their responsiveness to an agonist. This occurs through several processes. You can imagine how a structural change in a receptor would make it less effective. A modified receptor may be able to bind an agonist, but the bound agonist is unable to induce a response.
________pathways into smaller, separate components called modules. This means that an individual ligand-receptor interaction can involve multiple modules; that is, it can activate multiple downstream signaling cascades.
Modularity refers to the breakdown of signal transduction pathways into smaller, separate components called modules. This means that an individual ligand-receptor interaction can involve multiple modules; that is, it can activate multiple downstream signaling cascades.
When _____ binds to its receptor, the receptor activates two distinct signaling cascades. One is the phosphoinositide-3 kinase pathway and the other is the RAS/MAP kinase pathway (
insulin
_______ occurs when certain signaling pathways are regulated by the activation of multiple receptors. For example, the MAP kinase pathways can be regulated by both G protein–coupled receptors and growth factor receptor kinases. This “cross-talk” allows the cell to integrate many different external stimuli into particular and focused patterns of cellular response. So the response of a cell to a particular signal can depend on what other signals are acting on it, thereby integrating multiple signals.
Integration
Amplification of a signal is accomplished through ______. Receptors with direct activity include ligand-gated ion channels and nuclear receptors.
Secondary messengers
_____ is the process of conveying molecular signals from the outside of a cell to the inside of the cell.
Signal transduction is the process of conveying molecular signals from the outside of a cell to the inside of the cell.
First messengers are the molecules that start the process and reach the outside of the cell, such as _______: these are commonly referred to as ligands.
hormones and neurotransmitters
(True or False) Secondary messengers are intracellular molecules like cAMP (cyclic adenosine monophosphate) and cGMP (cyclic guanosine monophosphate) can bind and activate secondary receptors, triggering changes such as proliferation, differentiation, and apoptosis of the cell by binding to and activating secondary effectors.
True
G protein–coupled receptors (GPCRs) are membrane bound receptors that detect extracellular signals, primarily neurotransmitters and hormones, and convert them to intracellular responses through __________
signal transduction pathways.
GPCRs activate the _____pathway and the phosphatidylinositol pathway. GPCRs interact (couple) with G proteins, also known as guanine nucleotide–binding proteins, a family of intracellular proteins that act as signal transducers.
cAMP
G proteins are subdivided mainly into two different subtypes: ___________
trimeric G proteins and monomeric G proteins.
One GPCR-activated pathway is the ______ system. On activation of the GPCR via ligand binding, the receptor undergoes a conformational change that allows it to function as a guanine nucleotide exchange factor (GEF).
cAMP system.
(GEF) exchanges a bound GDP (guanosine diphosphate) for a GTP (guanosine triphosphate) within the _____ of its associated G protein.
Gα subunit
The Gα subunit dissociates from the GPCR and activates the nearby enzyme _____ (the primary effector) to create cAMP (the secondary messenger)
adenylate cyclase (the primary effector)
cAMP then activates_______, a secondary effector, amplifying further downstream effects.
protein kinase A (PKA)
The Gα subunit has an intrinsic GTPase, which hydrolyses the GTP back to GDP, allowing Gα to re-associate with the GPCR and turn ___
off
It is worth mentioning that trimeric G proteins can have an inhibitory or stimulatory action. Classically the stimulatory α subunit activates cAMP, and the inhibitory α subunit inhibits the production of _____
cAMP.
The other important GPCR-activated pathway is the ______ system
phosphoinositol (IP3/DAG) system
On activation of the GPCR via ligand binding, phospholipase C (primary effector) is turned ___
on.
IP3 cleaves a phospholipid from the plasma membrane, which releases the secondary messengers inositol triphosphate (IP3) and diacylglycerol (DAG).
True
IP3 stimulates release of ______ from the endoplasmic reticulum (called the sarcoplasmic reticulum in muscle cells).
calcium
DAG activates the secondary effector protein kinase C, which binds both Ca2+ and ______phosphatidylserine in the membrane, activating various downstream targets.
phosphatidylserine
Receptor tyrosine kinases (RTK)
Receptor tyrosine kinases (RTK) are high-affinity cell surface receptors that bind to various growth factors, hormones, and some cytokines. Receptor activation causes dimerization and autophosphorylation. The receptor can then activate monomeric G proteins, which recruits a guanine nucleotide exchange factor. This protein, in turn, can activate additional small G proteins (secondary messengers), ultimately leading to activation of transcription factors (secondary effectors). Classic examples of small G proteins are Ras, Raf, and Rho. Because RTKs usually stimulate cell growth, they are often altered in cancer. RTKs may acquire mutations that allow them to be constitutively active or overexpressed.
Receptor tyrosine kinases are an attractive target for drug therapy. Various small molecule inhibitors have been used in the clinic, such as imatinib for chronic myeloid leukemia. Antibodies have also been developed for RTKs with trastuzumab against the HER2 (ErbB2) receptor as a classic example.
Monomeric G proteins are also an area of interest for anticancer drug development because aberrant cell signaling is involved in the carcinogenesis process. Ras itself has been proven a challenging protein to target. However, some kinases in the downstream cascade, like Raf, have been targeted successfully with multi-kinase inhibitors such as sorafenib.
Calmodulin
Calmodulin is a ubiquitous calcium binding protein that can bind to a multitude of different protein targets and affect many different cellular functions. Calmodulin mediates different process like inflammation, metabolism, apoptosis, muscle contraction, etc.
A… Lipophilic hormones generally alcohols or ketones so many of their names end in -ol or -one
B
Guanylate cyclase
Guanylate cyclase is an intracellular enzyme that acts as both the signal transducer and primary effector for nitric oxide, a potent vasodilator. On activation of guanylate cyclase via ligand binding, the secondary messenger cGMP is formed from GMP. Similar to cAMP, cGMP activates a protein kinase called protein kinase G (secondary effector), amplifying further downstream effects.
Which of the following best describes where the central axon process of a primary somatosensory nerve can be found?
Between the soma and the dorsal horn. This is the correct answer. Although the axon appears to be continuous from the sensory organ or free nerve endings to the dorsal horn, once past the region of the soma the process is called the central axon. This process is generally much shorter than the peripheral nerve process because the cell bodies lie in the dorsal root ganglion, close to the spinal cord dorsal horn. TAKEAWAY: Free nerve endings and other somatosensory neurons (such as those attached to Pacinian corpuscles, Merkel discs, etc.) have a distal neural tube with a distal neurite. At the first node of Ranvier the peripheral axon truly begins, and run as a continuous fiber all the way to the dorsal horn where it synapses onto secondary neurons or interneurons. Once past the region of the soma, which resides in the dorsal root ganglion, the process is considered central.
first-year medical student is studying the various ion gradients and permeabilities of epithelial cells. Which of the following would cause an immediate reduction in the amount of potassium leaking out of a cell?
Hyperpolarizing the membrane potential – This is the correct answer. Hyperpolarizing the membrane makes the inside of the cell more negative and therefore makes it more difficult for potassium to flow out of the cell. According to the Nernst equation, the electrical gradient for K + is inward and the concentration gradient is outward. TAKEAWAY: The amount of potassium leaking out of the cell depends on its membrane potential, its concentration gradient, and its membrane conductance.
Which of the following best describes the trigger area for firing an action potential for a Pacinian corpuscle (lamellar corpuscle)?
First node of Ranvier. This is the correct answer. If enough depolarizing signal arrives from the nerve fiber in the lamellar layers of the distal nerve (analogous to a dendrite), then an action potential will fire and travel along the single process to the dorsal horn. TAKEAWAY: For many sensory neurons, the first node of Ranvier acts as the trigger region for decisions about AP generation, similar to the initial segment in multipolar cells.
SER
Endocytosis
D SER
B…RER
Cell adhesion
