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 to bind to apoptosis inhibitory protein;Bad protein is mutated such that it is able to bind with 14-3-3 protein without phosphorylation / permanently;

2018 / H2 / EJC PRELIM / P2 Q73Fig. 7.1 shows a CREB (cAMP response element binding) signalling pathway. This pathway is triggered when ligand X binds to a receptor at the cell membrane. CREB proteinFig. 7.1(a)With reference to Fig. 7.1, (i)Describe precisely the structure of the G protein coupled receptor and explain how the described structure enables it to perform its function.………………………………………………………………………………………………………………………………………………………………………………………………………………………………

……………………………………………………………………………………………………………………………………………………………………………………………………………………………[2]1.GPCR is a receptor protein with seven transmembrane domains, consisting of hydrophobic regions forming hydrophobic interactions with the hydrophobic fatty acid tails/nhydrophobic core of the phospholipid bilayer;2.Allows GPCR to be embedded on the cell surface membrane to allow it bind/ interact with hydrophilic/ polar/ large/ charged ligand; OR3.GPCR has an extracellular ligand-binding site that is complementary in shape and charge to the ligand allowing ligand to bind 4.to induce conformational change in intracellular domain of receptor leading to signal transduction;OR5.GPCR has an intracellular domain that associates with a G-protein;6.Change in conformation of intracellular domain of receptor leading to signal transduction;(ii)Describe how protein kinase A (PKA) is activated. ……………………………………………………………………………………………………… ……………………………………………………………………………………………………… ……………………………………………………………………………………………………… …………………………………………………………………………………………………...[2]1.cAMP binds to 2 subunits of inactive protein kinase A;2.the remaining 2 subunits dissociate and become activated protein kinase A;(iii)State the role of PKA in this signaling pathway? ……………………………………………………………………………………………………… …………………………………………………………………………………………………...[1]1.To phosphorylate the CREB protein so that co-activator can bind to it.

(b)CREB is an activator protein that binds to its specific control element to upregulate the transcription of the target gene.Explain how an activator protein like CREB can upregulate transcription of a gene.……………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………[3]1.CREB will bind to its enhancer on DNA;2.causing the spacer DNA between the promoter of the gene and enhancer to bendORRecruit histone acetylase / chromatin remodelling complex to decondense chromatin;3.Thus promoting the assembly of RNA polymerase and general transcription factors at the promoter to form transcription initiation complex;(c)CREB is known to be involved in other signaling pathways. With reference to Fig. 7.1 or otherwise, suggest how it is possible for CREB to bind to other control elements so as to regulate the transcription of different genes.……………………………………………………………………………………………………………………………………………………………………………………………………………………………[1]1.CREB protein can be phosphorylated at different sites by PKA, leading to different conformation changes that allow CREB to bind to different control elements;

2.Different co-activators may be recruited and bind to CREB, leading to different conformation changes that allow CREB to bind to different control elements;(any one)[Total: 9]

2018 / H2 / MJC PRELIM / P2 Q6QUESTION 4STAT proteins are cytoplasmic transcription factors that play important roles in the development and differentiation of many cell types. Upon external stimulation, STAT protein is activated from its inactive form and binds to another activated STAT protein to form a dimer. This protein dimer then translocates to the nucleus and regulates the expression of other genes as shown in Fig. 6.1. Fig. 6.1(a)With reference to Fig. 6.1, (i)explain how the inactive STAT protein is converted to its active form. [2]Via Post-Translational modification / phosphorylation ATP is hydrolysed to donate a phosphate group to the inactive STAT to form an active STAT protein.(ii)besides converting the inactive form of STAT protein to its active form, describe how the level of the inactive STAT protein may be controlled after its production. [2] These inactive forms of STAT may be tagged with ubiquitin proteins which are recognized by and degraded in proteasomes This decreases concentration / amount of STAT

STAT5 gene, a member of the STAT family, is widely expressed in hematopoietic stem cells (HSC) to regulate the self-renewal and differentiation of the stem cells. Fig. 6.2 shows the differentiation of HSC leading to the formation of different cell types such as T cell and B cell. Fig. 6.2(b)Explain how the different cell types such as T cell and B cell can arise from a sing