Ligand Cell Biochemistry

1- (30 pts) There are many stages after transcription which regulate gene expression. What are these additional regulatory mechanisms? Describe each of these stages.

These drugs were utilized in order to demonstrate the positive and negative effects on cell communication. Cell communication consists of three steps: reception, transduction, and response. Reception involves the binding of a ligand and a receptor; transduction is a “cascade” of actions between molecules and their proteins, and response is the change that occurs afterwards (1).

In a cell cycle, there are specific checkpoints between each phases caused by the occurrence of cyclin. Cyclin determines how concentration flunctuatues. If the regulation is disrupted by a decreasein cyclin, there would be no mitosis, meaning the cell cycle would continuously go thre G0 phase. However, if there is an increase

24.Which of the following are common means by which binding of an intercellular chemical messenger with a cell’s receptor brings about an intracellular response?

The insulin signaling cascade is initiated when insulin binds to insulin receptors located on the cell 's surface. The insulin receptor has four subunits: two alpha subunits located on the outside of the cell and two transmembrane beta subunits (3 & 4). When insulin binds to the alpha subunit receptors, it transmits a signal across the plasma membrane and activates tyrosine residues that are attached to the beta subunits. The activation of the tyrosine residues causes it to autophosphorolate and then phosphorolate other proteins that also have tyrosine residues attached to them. These phosphorylated proteins then move on to trigger cellular responses such as translocation of GLUT4 vesicule to the cell membrane. The vesicule becomes a transporter to allow glucose to come into the cell so that it can continue on and be stored as glycogen (3).

Changes in the concentration of small molecules, called second messengers, constitute the next step in the molecular information circuit. Particularly important second messengers include cyclic AMP and cyclic GMP, calcium ion, inositol 1,4,5-trisphosphate, (IP3), and diacylglycerol. The use of second messengers has several consequences. First, second messengers are often free to diffuse to other compartments of the cell, such as the nucleus, where they can influence gene expression and other processes. Second, the signal may be amplified significantly in the generation of second messengers. Enzymes or membrane channels are almost always activated in second-messenger generation; each activated macromolecule can lead to the generation of many second messengers within the cell. Thus, a low concentration of the signal in the environment, even as little as a single molecule, can yield a large intracellular signal and response. Third, the use of common second messengers in multiple signaling pathways creates both opportunities and possible problems. Input from several signaling pathways, often called cross talk, may affect the concentrations of common second messengers. Cross talk permits more finely tuned regulation of cell activity than would the action of individual independent pathways. However, unsuitable cross talk can cause second messengers to be

c. communicating – when a substance from one cell generatesthe transport of chemicals across the plasma membrane of another cell. This may make action potential possible.

Cells likewise speak with each other all the more straightforwardly through the items that they discharge. For example, a neuron cell transfers an electrical heartbeat using neurotransmitters . The neurotransmitters are put away in vesicles and lie beside the cytoplasmic face of the plasma layer. At the point when the proper flag is given, the vesicles holding the neurotransmitters must reach the plasma film and emit their substance into the synaptic intersection, the space between two neurons, for the other neuron to get those neurotransmitters.

This process called the “uncoupled”. “Down regulation” means the receptor mRNA and protein synthesis decrease and the preexisting receptor degradation. The “uncouple” and “down regulation” are both involved in the receptor desensitization, but in different steps. These steps are following described. First, the receptor uncouple from heterotrimeric G proteins; Second, cell surface receptors internalize into intracellular membranous compartments; Third, receptor mRNA and protein synthesis decrease result in the down regulation of the total cellular complement of receptors, as well as both the lysosomal and plasma membrane degradation of pre-existing receptors.

There are four types of receptors. The primary function of the receptors is to bind to the ligand. Receptors recognize specific ligand. Receptors only bind to only one or few ligands and allow them to transmit a signal into the cell. The common receptors at the cell-surface are Gated Ion Channels, transmembranous receptors, and G-Protein receptors.

This signaling cascade starts with an extracellular ligand (most likely a growth factor or cytokine) binding to JAK receptors which causes dimerization3. The JAK receptor monomers are bound to inactive JAK (Janus kinase which is a tyrosine kinase therefore, it only phosphorylates tyrosine residues) but when dimerized JAK is activated and trans-phosphorylates the receptor which leads to protein recruitment2,3. This is an example of a writer protein (JAK) add a PTM (phosphate) onto another protein (JAK receptor) and as a result, moves the pathway forward by recruiting other proteins. JAK also phosphorylates the recruited proteins including a transcription factor called STAT3. Once active, STAT dimerizes with another activated STAT protein then enters the nucleus3. Dimerization occurs via the SH2 (Src Homology 2) domain which can recognize and bind to phosphotyrosines3. This is an example of a reader protein domain (SH2) recognizing and binding to a PTM (phosphate) on another protein (STAT) and as a result, moves the pathway forward by causing dimerization. Then the dimer binds to specific gene elements to influences

Protein tyrosine kinase is an enzyme that catalyzes the transfer of the γ phosphate of ATP to tyrosine residues on protein substrates. Phosphorylation of proteins by kinases is an important mechanism in signal transduction and regulating cellular activity, such as cell division. Tyrosine phosphorylation is a key covalent modification that occurs in multicellular organisms as a result of intercellular communication during embryogenesis and maintenance of adult tissues. Phosphorylation of tyrosine residues modulates enzymatic activity and creates binding sites for the recruitment of downstream signaling proteins [2].

The first part of this process is called transcription, where the DNA of a gene is turned into mRNA. The second part of this process, translation, is where the mRNA is turned into a protein. The transcription process is regulated by small proteins called transcription factors. The location of the transcription factors' binding to DNA, determines which genes the cell expresses. Different transcription factors are operating actively in different cell types, which causes different cell types to produce different proteins, which causes each cell to have a unique distinctive

RIG-I recognizes bacterial ligands in glial cells. RIG-I is traditionally viewed as a viral pattern recognition receptor, however, more recently the pathogen ligands for RIG-I have been expanded to include bacteria nucleic acids. In non-CNS cell types RIG-I has been documented to identify bacteria RNA directly or DNA indirectly via an RNA polymerase III dependent mechanisms. RIG-I dependent recognition of bacterial nucleic acids was demonstrated to be pathogen and cell type specific. In glial cells the role and mechanism of RIG-I in pathogen detection has not fully been explored. We have previously demonstrated expression of RIG-I and the contribution of RIG-I to recognition of RNA and DNA viruses. However, the requirement of RIG-I for

Receptor - is a body structure that monitors changes in a controlled condition and sends input in the form of nerve impulses to the control center Control