Exchange of GDP for GTP GDP GTP Inactive Ras GDP protein Active Ras GTP protein GTP hydrolysts Cancer-causing mutations that prevent GTP hydrolysis keep Ras protein in the active state. FIGURE 25.12 Functional cycke of the Ras protein. The binding of GTP to Ras activates the function of Ras and promotes cell division. The hydrolysis of GTP to GDP and P; converts the active form of Ras to an inactive form. EGF receptor EGF Sos Ras Sos GRB2 Ras Raf-1 GDP GTP GRB2 Raf-1 GDP MEK MEK MAPK MAPKB Exposure to EGF Jun Jun -P Myc Fos Myc Fos -P Epidermal cell Pathway off Pathway on FIGURE 25.11 The activation of a cell-signaling pathway by a growth factor. In this example, epidermal growth factor (EGF) binds to two EGF receptors, causing them to dimerize and phosphorylate each other. An intracellular protein called GRB2 is attracted to the phosphorylated EGF receptor, and it is subsequently bound by another protein called Sos. The binding of Sos to GRB2 enables Sos to activate a protein called Ras. This activation involves the release of GDP and the binding of GTP. The activated Ras/GTP complex then activates Raf-1, which is a protein kinase. Raf-1 phosphorylates MEK, and then MEK phosphorylates MAPK. More than one MAPK may be involved. Finally, the phosphorylated form of MAPK activates transcription factors, such as Myc, Jun, and Fos. This leads to the transcription of genes, which encode proteins that promote cell division.

GTP binding proteins are molecular switches. How do GTP binding proteins work? Provide two examples of GTP binding proteins that function in intracellular protein transport. Make a drawing that illustrates the function of each of these proteins in their respective roles. Predict the direct outcome of a mutation that: Inhibits GTPase activity Inhibits interaction with the GEF

Explain why in cells that are genetically NF1–/–, basal levels of GTP-bound activated Ras are higher than normal and respond to growth factor stimulation by increasing rapidly to far higher levels.

Predict the eff ect on cell growth of an Sos mutation that decreased its affi nity for Ras.

Match the protein on the left with the type of activation of that protein on the right STAT Smad PKA Ras NFKB Nuclear receptor [Choose] [Choose] GTP binding serine phosphorylation Interaction with Galpha Cleavage by y-secretase destruction of a protein by proteasome tyrosine phosphorylation second messenger ligand binding [Choose] [Choose] [Choose]

RGS proteins accelerate the GAP activity of Gα subunits.  What is the direct result of this GAP activity?  - hydrolysis of GTP, resulting in a GDP-bound Gα - phosphorylation of GDP to GTP, resulting in a GTP-bound Gα - an exchange of GTP for GDP bound to Gα - an exchange of GDP for GTP bound to Gα

Tumor necrosis factor (TNF) signaling Explain in detail each step in figure 8.53.  Make sure to include an explanation of the proteolytic and phosphorylation cascades.

The egfr kinase independent transactivation of the ras pathway does require egfr. Explain this apparent contradiction.

Cell signaling The maximum secretion rates of proteins are one type of limiting constraint on signal-ing processes since a cell cannot send a signal faster than it can secrete it. These maximum signalingrates can be estimated with maximum rates of transcription and translation. Consequently, proteins withstrong promoters can be synthesized at much higher rates. Immunoglobulins, which are important signal-ing molecules, have very strong promoters. Their maximum secretion rate is on the order of 2000 to 8000antibody molecules/cell/second, which corresponds to approximately 1 pg/cell/hr. Part AWhat would be the maximum signal (in pg/cell/hr) that a cell could send for the following situations: (1)Signal molecule A has a MW = 100,000 daltons and is secreted at a rate of 1000 molecules/cell/second. (2)Signal molecule B has a MW = 50,000 daltons and is secreted at 5000 molecules/cell/second.Part BWhich molecule is secreted at a higher rate? By how much?Part CIf equivalent fluxes of both…

Specificity in fusion between vesicles involves two discrete and sequential processes. Describe the first of the two processes and its regulation by GTPase switch proteins. What effect on the size of early endosomes might result from overexpression of a mutant form of Rab5 that is stuck in the GTP-bound state?