Question

a. Signals can be relayed, amplified, integrated, distributed, and regulated by feedback. Describe an example for each of these processes.

b. The above processes make for long and complicated signal transduction pathways. Why bother? (Describe how this can be advantageous for a cell)

c. Ras monomeric GTPase is a molecular switch regulated by GAPs and GEFs. If you were studying a mutant cell that had an inactive GAP protein, how would this affect Ras signaling?

Answer 1

Answer:

a) In a living system, for a signal to induce some desired effect on target, it has to be received using a protein called as recceptor protein. This binding is followed by downstream signal relaying, amplification (some receptors) and also regulated to complete the cycle. The signal binding to a receptor can be light, touch or heat (few instance) and ligands (in many cases). Ligands can be of hormones, peptides, amino acids, lipid derivatives, steroids etc.

The hydrophilic signal molecules lik proteins and peptides bind to receptors on the cell membrane whereas hydrophobic signals like steroids, retinoids etc crosses the membrane and binds to cytosolic receptors.

The amplification of signal is mainly obsreved with GPCR signaling. Here binding of a hormone triggers a conformational change in the receptor, leading to activation of a G protein by catalyzing the GTP exchange for GDP. The activated G protein, actvates downstream signaling by activating downstream activators. Activation of a single cell surface receptor protein can result in an increase in thousands of cAMP molecules or Ca2+ ions. These activated cAMP, each of these cAMP inturn activates its target ptotein kinases or other activators.

The desensitization of the receptor after the completion of signaling is equally important in these prossess. The downregulation of TGF-beta signaling using inhibitor SMADs like I-SMADs is an example for the desensitization of the receptor through negative feed back mechanism.

b) One common example for GPCR is the glycogen receptors that induce the degradation of glycogen to release glucose. Glucagon or epinephrine binding to specific GPCRs activate the downstream G-protein, This G-protein in their GTP bound conformation, activates adenylate cyclase that convrts ATP to cAMP. Many cAMP molecules actvatd in this pathway induce signal amlification by activating downstream kinases for a prolonged time. Final enzyme in this cascade the glycogen phosphorylase induces th degradation of gycogen. Signal amplification in these pathway is important in that certain biochemical prossess requires prolonge time for the actual completion of the prossess. This can only be executed through signal amplification.

c) Ras GTP is an important protein in MAP kinase signaling pathway. Here GTP bound activated Ras, inturn activates some downstream activators important for cellular proliferation. Mutation in GAP proteins which in normal condition helps convert Ras GTP to Ras GDP will cause serious effects in cellular homeostasis. Because this mutation maintains Ras in GTP bound conformation which activates downstream cellular proliferation even in the absence of signal. This may leads to cancer.

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