Ch. 14: Cell Signaling Online Quiz (Essay) Flashcards
What are the hallmarks of the first steps in signaling through receptor protein-tyrosine kinases?
Receptor protein-tyrosine kinases span the plasma membrane; upon binding by extracellular stimulants, they form dimers with one another and ___. The cytoplasmic domain can then bind and activate intracellular proteins containing ___ domains, which specifically bind peptides containing phosphotyrosine residues. The ___ domain-containing proteins then go on to activate a variety of different pathways depending upon the identity of the receptor that activated them.
autophosphorylate, SH2
In plants, growth can be mediated by what is frequently referred to as “auxin-induced transcription” of genes critical to growth. This terminology was derived from experiments demonstrating that the addition of auxin leads to an increase in the expression of genes responsible for growth. However, since auxin is not a transcription factor and cannot directly activate transcription, how does it regulate gene activity?
Many plant growth genes are constitutively or always repressed by proteins that bind DNA and inhibit transcription. Simply removing them will ___ the rate of transcription. Auxin binds to a receptor with ubiquitin ligase activity, which leads to the ubiquitination and subsequent proteolytic degradation of the repressor. Thus, even though auxin cannot directly affect gene expression, it can still have dramatic effects on expression by regulating proteins that do directly interact with the genes.
increase
What would happen to NF-κB signaling if IκB were unable to be dephosphorylated?
Most likely nothing. When IκB is ___ by IκB kinase, it is targeted for ubiquitination and then degraded by proteasomes. If it could not be dephosphorylated, it would still be targeted for ubiquitination and then degraded by proteasomes.
phosphorylated
Cytokine receptors frequently form dimers upon ligand binding, and these can be heterodimers or homodimers. Explain how this ability of the receptors to form different combinations of dimers allows three unique cytokines, each with a unique action, to arise from only two cytokine receptors.
If dimerization is required, then the two receptors (R1 and R2) could form homodimers (___:___ and ___:___) and potentially interact with two of the cytokines; the third cytokine could bind to a heterodimer of ___:___. Given the number of cytokines and receptors and the many combinations such as these that are possible, the complexity of these signaling networks becomes evident.
R1:R1, R2:R2, R1:R2
Growth factors and cytokines both lead to tyrosine phosphorylation through receptors, but they do so through different mechanisms. What is the key difference between the receptors for these two classes of ligands in terms of their tyrosine kinase activity?
The receptors for growth factors, such as EGF, are membrane-spanning cell surface receptors in which the cytoplasmic domain of the receptor contains the \_\_\_ activity necessary to phosphorylate proteins on tyrosine residues and often are capable of \_\_\_. Cytokine receptor activation also leads to tyrosine phosphorylation, but the receptor \_\_\_ \_\_\_ have intrinsic catalytic activity. Instead, upon ligand binding, the cytokine receptors interact with a class of proteins called nonreceptor tyrosine kinases, which in turn do have the catalytic activity necessary for tyrosine phosphorylation.
catalytic, autophosphorylation, DOES NOT
As a cell biologist for a pharmaceutical company, you are charged with developing a drug to inhibit the cAMP-cAMP response element binding protein (CREB) pathway. Briefly describe the cascade leading to CREB activation and where one might target a drug to block its activation.
In the presence of cAMP, the R subunit is bound by four molecules of cAMP, allowing the catalytic subunits to ___, translocate to the nucleus, and then phosphorylate CREB. CREB then ___, binds to the CRE (cAMP response element) in the promoter of target genes, and activates transcription.
A drug could stabilize the R and C subunit interactions of PKA and block translation into the nucleus. A drug could prevent interaction of cAMP with the R subunit and essentially lead to the same result. Similarly, a drug could have a more downstream action that might prevent phosphorylation of CREB, thus not allowing it to become activated. Another option would be to prevent the required dimerization of CREB, thus preventing its ability to bind DNA.
dissociate, homodimerizes
In the signaling of cells to initiate growth a host of genes designated immediate early genes become activated to initiate the growth process. What would happen to the the expression of these immediate early genes if Elk-1 was not able to to be dephosphorylated and why?
The immediate early genes would be constitutively activated (i.e., not shut off). Immediate early genes share the serum response element in their promoters that interact with serum response factor (SRF). Following the growth signal pathway ERK phosphorylates and activates Elk-1 that interacts with ___ and activates transcription of the immediate early genes. If it is unable to be de-phosphorylated it would remain active and continually express these genes and with it being a growth signal may well lead to cancer.
SRF
Explain the concept of “feedback loops” in signaling networks:
Feedback loops allow for a form of ___ of a particular event or activity. In signaling, there are positive feedback loops, in which a downstream element of the pathway activates an upstream element. The counterpart would be a negative feedback loop, in which a downstream element inhibits the activity of an upstream element, shutting down the pathway.
autoregulation
Why do enzymes that lie downstream of a cell surface receptor in a signal transduction pathway amplify as well as propagate the signal?
Extracellular signaling molecules typically stimulate only a single receptor molecule before being degraded; the receptor, however, can often activate ___ molecules of the enzyme to which it is directly linked. Since most signal transduction pathways are made up of several enzymes, amplification can occur at each step, resulting in very high amplification by the time the pathway reaches the ultimate component.
many
What is the basis for the different responses of nerve cells versus heart muscle cells to acetylcholine?
In nerve cells, the acetylcholine receptor doubles as a ligand-gated ion channel composed of five subunits. When bound by acetylcholine, the receptor opens to allow entry of ___ and exit of ___, thus depolarizing the membrane and triggering an action potential.
In contrast, in heart muscle, the acetylcholine receptor has a very different structure—it is a ___ ___ ___ which directly activates a ___ channel, causing the cardiac muscle to slow.
Na+, K+, G protein-linked receptor, K+
In what ways are steroid hormone receptors different from most other types of cellular receptors?
Most cellular receptors span the plasma membrane, where they are ideally positioned to sense extracellular signals and transmit them to the cell’s interior. In contrast, because steroid hormones are small hydrophobic molecules that can slip through membranes, their receptors are located in the interior of the cell, in both the ___ and the ___. In addition, once activated, the steroid hormone receptors themselves act as transcription factors, whereas for receptors located in the plasma membrane, the transcription factors usually lie at the end of a signal transduction cascade that includes several components.
cytoplasm, nucleus
