When Activated by the Extracellular Signal Protein Platelet-Derived Growth Factor

Essay

When activated by the extracellular signal protein platelet-derived growth factor (PDGF), the PDGF receptor phosphorylates itself on multiple tyrosines (as indicated in Figure 16-61A by the circled Ps; the numbers next to these Ps indicate the amino acid number of the tyrosine).These phosphorylated tyrosines serve as docking sites for proteins that interact with the activated PDGF receptor.These proteins are indicated in the figure, and include the proteins A, B, C, and D.One of the cell's responses to PDGF is an increase in DNA synthesis, which can be measured by the incorporation of radioactive thymidine into the DNA.
To determine which protein or proteins-A, B, C, or D-are responsible for the activation of DNA synthesis, you construct mutant versions of the PDGF receptor that retain one or more tyrosine phosphorylation sites.You express these mutant versions in cells that do not make their own PDGF receptor.In these cells, the various mutant versions of the PDGF receptor are expressed normally, and, in response to PDGF binding, become phosphorylated on whichever tyrosines remain.You measure the level of DNA synthesis in cells that express the various mutant receptors and obtain the data shown in Figure 16-22B. (A)


(B)


Figure 16-22
A.From these data, which, if any, of proteins A, B, C, and D are involved in the stimulation of DNA synthesis by PDGF? Explain your answer.
B.Which, if any, of these proteins inhibit DNA synthesis? Explain your answer.
C.Which, if any, of these proteins seem to have no detectable role in DNA synthesis? Explain your answer.