INTRODUCTION

A growth factor can trigger a cell to grow, differentiate, or divide. Many growth factors act by binding to a receptor on the cell's surface, causing the receptor to initiate a series of events inside the cell that lead to a cellular response, such as cell division. The sequence of molecular events and chemical reactions that lead to a cell's response is called a signal transduction pathway.

Signal transduction pathways are by necessity highly regulated. If a pathway triggered by a growth factor cannot turn off, for example, cells may continually divide without regulation—that is, become cancerous. In this animation we look at the events of one type of signal transduction pathway, as well as how a mutant protein (called Ras) in the cascade can result in cancer.

CONCLUSION

In the accompanying animation, we look at one type of signal transduction pathway. It begins with the binding of a growth factor to a protein kinase receptor. The activated receptor initiates a series of events that leads to the activation of the protein Ras, which in turn activates a protein kinase cascade, which ultimately results in a cellular response to the growth hormone.

Each activated member of the pathway must soon turn off to prevent abnormal cellular responses, such as uncontrolled cell division. Ras has a shut-off mechanism—it cleaves its bound GTP to form GDP, and thereby becomes inactive. Additionally, phosphatase enzymes turn off the protein kinases in the pathway by removing their activating phosphate groups.

About 20% of all tumors have an activating mutation in a Ras gene (and a number of other cancers have abnormalities in other aspects of signal transduction). Investigations have shown that such abnormal forms of Ras are always active because they are permanently bound to GTP, and thus cause continuous cell division. If the abnormal form of Ras is inhibited, cells stop dividing. A major effort is underway to develop specific Ras inhibitors for cancer treatment.

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Textbook Reference: Concept 5.5 The Membrane Plays a Key Role in a Cell’s Response to Environmental Signals