UNIT 8 - Signalling Flashcards
On a cell surface, why are there so many different types of receptors with binding specificities to different molecules?
There are many different receptors, because there are many different signals that a cell can receive. Many receptors with a binding specificity for many types of signals ensures that the cell can respond to a variety of environmental conditions or requirements in a coordinated fashion.
What are the three general steps in signal transduction?
a) signal binds receptor,
b) pathway of intermediates and reactions,
c) target cell response.
List two general ways that signal transduction causes a change or response in a cell.
a) influence gene expression,
b) influence intracellular proteins involved in metabolism or cellular function.
What is the structure of a ligand‑gated ion channel?
How does signal transduction occur through these receptors?
Ligand‑gated ion channel receptors are membrane receptors that are made up of multiple transmembrane proteins to create a pore or a channel in the membrane.
These are specific for a particular ion, and allow the movement of only one ionic species.
Examples of ions are Na+, K+, Ca2+, and Cl−. A signal is recognized by the ligand‑gated ion channel receptor, and the channel opens to allow the passage of an ion.
The presence of the ion in the intracellular environment induces a response. An example is in cells in neuromuscular junctions.
This type of signal transduction is rapid.
Why is signal transduction through ligand‑gated ion channel receptors very rapid?
there are no pathways involved or intermediates and second messengers.
The binding of the signal to the receptor induces an influx of a particular ion and changes the cell environment quickly, causing a response.
How does acetylcholine transmit signals to muscle cells?
Acetylcholine binds the receptor on muscle cells, opening the channel to release Na+ and K+. This change in electric potential leads to muscle contraction.
What signals do nuclear receptors recognize?
How do these receptors transduce signals?
Nuclear receptors recognize hormones. These receptors are found in the cytoplasm of the cell, where they are bound to proteins such as HSP (heat shock protein). In this form, they are inactive. When they are bound by a hormone, they dissociate from the protein they were bound to and translocate into the nucleus, where they act as transcriptional regulators and influence the expression of target genes. They do this by binding to the regulatory sequences of the target genes called hormone response elements (HRE). This type of signal transduction is slower.
Why do steroid hormones such as testosterone and estrogen bind intracellular receptors?
they are hydrophobic and are unable to cross the membrane.
Why are individuals who have an abundance of nuclear receptors specific for estrogen more susceptible to tumorigenesis?
a) binding of estrogen to more receptors stimulates proliferation of mammary cells with an increase in cell division and DNA replications, leading to mutations; and
b) estrogen metabolism produces genotoxic waste, which results in disruption of the cell cycle, apoptosis, and DNA repair in cells, and promotes tumour formation.
Describe the structure of a G‑protein coupled receptor (GCPR).
G‑protein coupled receptors (GCPRs) are associated with a G‑protein (guanine nucleotide binding protein) on the cytosolic side of the membrane. GCPRs are located in the membrane and have seven transmembrane loops. One end of the receptor has an external domain that binds the signal outside of the cell; the other end, in the cytoplasm, interacts with a G‑protein to initiate the signal transduction pathway. Once the signal binds the receptor on the outer side of the membrane, the receptor undergoes a conformational change, which allows it to interact with a G‑protein on the inside of the membrane.
In the absence of a signal, a G‑protein in the cell has three subunits, αβγ. What happens to these G‑protein subunits in the presence of a signal?
In the presence of a signal, the GCPR undergoes a conformational change allowing the cytosolic end to interact with the G‑protein.
The three subunits of a G‑protein separate because the α subunit loses its GDP and binds to GTP and then dissociates from the βγ subunits.
The α subunit and the βγ subunits can then interact upon targets in the cell.
How can ion‑gated channels be activated through a GCPR?
Instead of a signal molecule interacting with an ion‑gated channel receptor directly, signal molecules can bind GCPRs, which lead to activation of a G‑protein that binds and opens an ion channel, resulting in changes in the membrane potential of the cell and a response by the cell.
Outline the signal transduction pathway and cell response to the signal epinephrine.
Binding of epinephrine to its GCPR leads to activation of a G‑protein. Protein kinase A (PKA) is activated and phosphorylates the enzyme glycogen phosphorylase. This activates the enzyme, which allows the cell to break down glycogen releasing glucose for use by the cell.
How does phospholipase C (PLC) initiate a signal transduction cascade resulting in increased transcription of target genes?
Phospholipase C (PLC) initiates a signal transduction cascade resulting in increased transcription of target genes in this manner:
Target binds GCPR and the receptor undergoes conformational change which allows it to interact with G‑protein.
G‑protein subunits are activated and dissociate (α subunit binds GTP instead of GDP).
α subunit activates PLC, which cleaves phosphatidylinositol 4, 5 bisphosphate (PIP2) into inositol triphosphate (IP3) and diacylglycerol (DAG).
IP3 and DAG work together to activates protein kinase C. IP3 diffuses to endoplasmic reticulum and causes Ca2+ release and this action along with DAG activates PKC. The Ca2+ release also causes direct cellular changes.
PKC phosphorylates a number of proteins which leads to the activation of different transcriptional regulators which move to the nucleus and initiate the transcription of particular genes.
Describe the structure of a receptor tyrosine kinase (RTK).
Receptor tyrosine kinases (RTKs) have an extracellular domain that binds the signal, and an intracellular domain involved in activation of signal transduction. These regions are connected by a transmembrane α‑helix. When a signal binds an RTK, it associates with another RTK and the two intracellular domains autophosphorylate tyrosine residues on the cytoplasmic tails of each other.
What is the function of Ras? How is this protein similar to a G‑protein?
Ras is a signaling protein that is similar to a G‑protein because it is a monomeric guanine nucleotide binding protein on the cytosolic face of the plasma membrane. It binds GDP in the absence of a signal (inactive) and GTP in the presence of a signal (active). It is also like a G‑protein because it can hydrolyze GTP.
The binding of insulin to its receptor triggers two pathways. Outline each one and indicate the cell response for each.
The insulin transduction pathway is influenced by feeding versus fasting states, hormones, and stress levels. When carbohydrates are consumed, the rise in blood glucose causes the pancreas to release insulin. When insulin binds its RTK (insulin receptor), it leads to two cascades:
MAP kinase: Binding of insulin to RTK causes association of two RTKs and tyrosine kinase activity (autophosphorylation) of cytoplasmic tails. The tails serve as binding sites for signaling proteins. One of these interacts with Ras and activates it by stimulating the exchange of GDP for GTP. Ras triggers a phosphorylation cascade of three MAP kinases (mitogen activated protein kinases). The final MAP kinase phosphorylates target proteins such as enzymes and transcriptional activators which affects cell differentiation and mitogenesis.
PI‑3K (phosphoinositide 3‑kinase). Binding of insulin to RTK causes association and activation of Ras as described above. Ras activates PI‑3K, which results in either the storage of usage of glucose through GLUT‑4 vesicle. GLUT‑4, which is responsible for passive diffusion of glucose, binds to PI‑3K after bringing glucose into the cell. The PI‑3K isolates the glucose, which is sent to the mitochondria to make ATP. The excess glucose is stored in the cell as glycogen. Signaling and activation of PI‑3K can also trigger a pathway that influences the synthesis of lipids, proteins, and cell survival and proliferation.
