2018_Cell-Signalling_STQ_MS

2018 Cell Signalling STQ MS2018 / H2 / ACJC PRELIM / P2 Q21Fig. 2.1 shows the activation of a G-protein linked receptor (GPLR) found in the cell surface membrane upon binding of a drug, salbutamol. Salbutamol is often used in the treatment of asthma – a long-term condition which narrows the airways in the lungs. The G protein consists of three subunits - α, β, and γ. Fig. 2.1(a)Describe how GPLR is held within the cell surface membrane.1.Hydrophobic interactions occur between the hydrophobic core/hydrocarbon tails of phospholipid bilayer and hydrophobic R groups of amino acid residues of GPLR;2.Hydrogen/ionic bonds formed between charged/ hydrophilic phosphate heads of phospholipids and hydrophilic R groups of amino acids in cytoplasmic + salbutamolGPLRadenyl cyclase dilation of airways ATPcyclic AMPactiveikiAinactiveprotein kinase Ainactiveprotein kinase BactiveproteinkinaseB cell surfaceb

extracellular regions of GPLR;[2](b)With reference to Fig. 2.1, describe how the use of salbutamol can relieve symptoms of asthma. 1.Binding of salbutamol to a specific/complementary binding site of GPLR result in conformational change of receptor;2.Activated GPLR activates G protein, where GTP replaces GDP;3.α subunit dissociates from βγ subunits;4.α subunit binds to and activates adenyl cyclase (at the membrane), which catalyses the conversion of ATP to cAMP;5.cAMP act as second messengers and activates protein kinase A;6.trigger a phosphorylation cascade resulting in amplification of signal, causing to dilation of airways;(c)There are many different types of receptors used by a cell to transduce extracellular signals. Some are located on the cell surface membrane while others are located within the cell. Explain why some receptors are found on the cell surface membrane while others are found within the cell. 1.Ligands which are lipid-soluble/hydrophobic/non-polar bind to specific nuclear receptors within the cell;2.Ligands which are not lipid-soluble/hydrophilic/charged/polar bind to specific receptors on the membrane;3.Ref to size;[2][4] [Total: 8]

2018 / H2 / DHS PRELIM / P2 Q3Question 2(a)ALigand IGF1 binds to the receptor tyrosine kinase. The receptor cross-phosphorylates each other and becomes activated; PI 3-kinase binds to the phosphorylated region of receptor tyrosine kinase and becomes activated. Activated PI 3-kinase phosphorylates and activates PI(4,5)P2;BPhosphorylated PI(4,5)P2 / PI(3,4,5)P3 serves as a docking site at the cell surface membrane. PDK1 and Akt binds to the PI(4,5)P3.;Akt is phosphorylated by activated PDK1 and mTOR. Akt becomes activated and dissociates from PI(3,4,5)P3 to phosphorylate Bad / causes Bad to bind to 14-3-3 protein;(b) (i)PI 3-kinase is mutated to become locked in the active state / resistant to phosphatases catalysis;Activity of PI 3-kinase increases / pathway always switched on;(b) (ii)Bad protein is mutated such that the conformation of active site involved in binding is changed / unable