Place the signaling components in the activation order for a proper mitogen-activated protein kinase (MAPK) signaling cascade:1.    Mek2.    Ras3.    Erk4.    Raf5.    Transcription regulatory proteins downstream of mitogen-activated protein kinase (MAPK) that lead to changes in gene expressionGroup of answer choices2, 4, 1, 3, 52, 4, 1, 5, 32, 4, 3, 5, 11, 3, 2, 4, 51, 3, 4, 2, 5

Kinases are essential in the cell because they...  1. help regulate protein function through changes in protein phosphorylation status.   2. are enzymes that denature damaged proteins.  3. destroy second messengers, thereby turning off a signal transduction pathway.  4. provide a mechanism for amplifying the effect of the original signaling molecule.Group of answer choices122 and 31 and 4All of 1-4 PreviousNext

Which of the following is (are) associated with the activation of transcription?Group of answer choicesChromatin remodeling.Histone acetylation.RNA polymerase recruited to the promoter.Transcription factors recruited to the (eukaryotic) promoter.All of the above.

Ras is a family of small cytosolic G proteins, signaling molecules that play a central role in cell growth and division.  Like other G proteins, Ras binds guanine nucleotides.  When Ras binds GDP, it is inactive.  In contrast, Ras-GTP—which is considered its active form—binds and activates downstream effectors such as Raf, a mitogen-activated protein kinase kinase kinase (MAPKKK).  Raf activation leads to a phosphorylation cascade that results in upregulation of genes related to cell growth and division.  In addition to its functional role as a mediator of cell signaling, Ras, like other G proteins, has intrinsic hydrolase activity and eventually hydrolyzes the bound GTP.Owing to its role in cell division, Ras mutations are implicated in many cancers.  ARS-853 is a recent mutation-specific anti-Ras drug that targets the oncogenic G12C mutant when an acrylamide functional group on ARS-853 reacts with the mutant cysteine residue (Figure 1).  Although the thiol–acrylamide reaction chemistry is well characterized, biochemical characterization of the drug's interaction with RasG12C is limited, hindering development of future inhibitors.Figure 1  Reaction of a thiol with an acrylamideExperiment 1NMR chemical shifts were measured at different pH values and at different concentrations of ARS-853.  The pKa of the Cys12 thiol was found to be lowered from 8.0 (the pKa of free cysteine) to 7.6 in RasG12C.  The Kd for ARS-853 interactions with RasG12C was measured as 36.0 ± 0.7 μM and was not significantly pH dependent.Experiment 2A fluorescent amino acid was added to RasG12C at a position far away from the ARS-853 binding site.  The change in fluorescence intensity over time upon addition of ARS-853 was measured.  Two time constants were calculated from the fluorescent decay signal, consistent with a two-step reaction mechanism of binding followed by covalent attack.Huynh, M. V., Parsonage, D., Forshaw, T. E., Chirasani, V. R., Hobbs, G. A., Wu, H., Lee, J., Furdui, C. M., Poole, L. B., & Campbell, S. L. (2022). Oncogenic KRAS G12C: Kinetic and redox characterization of covalent inhibition. The Journal of biological chemistry, 298(8), 102186. Question 35The two time constants measured in Experiment 2 were τD and τI.  These time constants were pH dependent and pH independent, respectively.  One of these constants represents noncovalent binding between ARS-853 and RasG12C, while the other represents the cysteine residue nucleophilically attacking ARS-853.  Based on the information in the passage, the most likely interpretation is that:A.τD represents the ligand binding reaction and τI represents the nucleophilic attack.B.τD represents the nucleophilic attack and τI represents the ligand binding reaction.C.The time constants represent ligand binding and nucleophilic attack but cannot be assigned without further information.D.the time constants cannot be specifically correlated to ligand binding or nucleophilic attack because the fluorescent amino acid is far away from the binding and attack site.

The kinase that phosphorylates a receptor tyrosine kinase (RTK) is:Group of answer choicesRasMAP kinaseRTK itselfAkt

Give a brief overview on the signaling pathway in human system.