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1. Imagine a prototypical receptor tyrosine kinase signaling pathway that leads

ID: 208229 • Letter: 1

Question

1. Imagine a prototypical receptor tyrosine kinase signaling pathway that leads to unwanted cellular proliferation and tumorigenesis when its expression increases in the cell; the cartoon below illustrates a basic schematic of such an RTK signaling pathway. Using your knowledge of RTK pathways, identify the typo in this figure that was published in a reputable journal. Hint: it involves switching between 2 states a) Growth factor b) Using 1-2 sentences to explain your logic for each part, describe whether ththerapeutic approaches below might be Tyrosine kinase receptor effective in reducing signal transduction from the oncogenic RTK to the nucleus. DRK (GRB2) SOS i) A non-hydrolyzable ATP analog GDP that binds selectively to the ATP site in your receptor kinase domain (ie. the terminal phosphate cannot be transferred to a substrate) RAF-MAPKKK ii) A viral expression therapy that R (MEKMAPKK drives constitutive expression of high levels of a Ras-specific GAP in the cell. ERK)-MAPK ii) A cell-permeable peptide mimetic that disrupts recruitment of the MAP kinase kinase to its scaffold protein KSR. Transcription (for example of phyllopod) iv) Which of these therapeutic approaches might be the most specific for attenuating signaling by your aberrantly expressed receptor tyrosine kinase? Explain your logic with one sentence. Nature Reviews | Genetics

Explanation / Answer

a. In this signalling pathway growth factor acts as a signal molecules and binds to the receptor tyrosine kinase receptor. by the binding of signalling molecule growth factor tyrosine molecule of receptors become phosphorylated and then activates the DRK GRB 2 proteins.

these proteins are associated with SOS.

GAP aur GTPase activating protein activates another protein.

RAS activates another protein which is RAF and do phosphorylation of it. it is also known as mitogen-activated protein kinase kinase kinase.

This MAPKKK qcts on DSOR or MEK. kindness is an enzyme which transfers phosphate group from one molecule to another molecule. by the process of phosphorylation proteins are activated. Due to activity of MEK rolled proteins are activated and move towards the nucleus.

These proteins move to the nucleus and activates the genes for the formation of RNA.

b.

1. phosphorylation is a process of adding phosphate from 1 molecule to another molecule. shear force with molecule is obtained from ATP and transferred to another proteins which are involved in signalling pathway.

phosphorylation of proteins make activation of those proteins and then continuous the signalling pathway for cell division.

when non hydrolysable ATP analogue binds to the enzyme kinase so not able to produce phosphate group. when phosphate group is not produced then not able to transfer from ATP to another protein.

so when ATP analogue which is not able to produce phosphate group is binds to the enzyme then protein cannot phosphorylated and then signalling pathway are not able to continue.

2. when high level of RAS specific GTPase activating protein are expressed and sell them the activation of RAS protein increases which leads to constitutive expression of genes by signalling pathway.

3.

when mitogen-activated protein kinase kinase are not able to interact with KSR then signalling pathway is not able to continuous for activation of further proteins. Hence reduction in signalling pathway which leads to reduction in gene transcription and cell division.

4.

in my opinion option first use of ATP analogue is most appropriate for controll of signalling process. By this we can control the signal in process but in another way when we see the condition of cell in which we have to replace all ATP with ATP analogue.

when all ATP of cell is replaced by ATP analogue than other activities of cell also affected.