1. Response: Cell signaling leads to regulation of transcription or cytoplasmic activities Chapter 11.4

2. Nuclear and Cytoplasmic Responses  Ultimately, a signal transduction pathway leads to regulation of one or more cellular activities.  The response may occur in the cytoplasm or in the nucleus.  Many signaling pathways regulate the synthesis of enzymes or other proteins, usually by turning genes on or off in the nucleus.  The final activated molecule in the signaling pathway may function as a transcription factor. Growth factor Receptor Reception Transduction CYTOPLASM Response Inactive transcription factor Active transcription factor DNA NUCLEUS mRNA Gene Phosphorylation cascade P

3.  Other pathways regulate the activity of enzymes rather than their synthesis.  This directly affects proteins that function outside the nucleus.  Example: a signal may cause the opening or closing of an ion channel in the plasma membrane or a change in cell metabolism.  Signaling pathways can also affect the overall behavior of a cell, for example, changes in cell shape  Some pathways lead to cell division.  The molecular messengers that initiate cell division pathways include growth factors and certain plan and animal hormones.  Malfunctioning of growth factor pathways may lead to cancer.

4. Fine-Tuning of the Response  Whether the response occurs in the nucleus or in the cytoplasm, it is not simply turned “on” or “off.”  There are four aspects of fine-tuning to consider:  Amplification of the signal (and thus the response)  Specificity of the response  Overall efficiency of response, enhanced by scaffolding proteins  Termination of the signal

5. Signal Amplification  Enzyme cascades amplify the cell’s response.  At each catalytic step in the cascade, the number of activated products can be much greater than in the preceding step.  The amplification effect stems from the fact that these proteins persist in the active form long enough to process multiple molecules of substrate before they become inactive again.  Example: Epinephrine  When epinephrine binds to a receptor on liver or muscle cell, glycogen is broken down into glucose.  A small number of epinephrine molecules binding to receptors on liver cell or muscle cell can lead to hundreds of millions of glucose molecules from glycogen.

6. The Specificity of Cell Signaling and Coordination of the Response  Different kinds of cells have different collections of proteins.  These different proteins allow cells to detect and respond to different signals.  Even the same signal can have different effects in cells with different proteins and pathways. Signaling molecule Receptor Relay molecules Response 1 Cell A. Pathway leads to a single response. Response 2Response 3 Response 4 Response 5 Activation or inhibition Cell B. Pathway branches, leading to two responses. Cell C. Cross-talk occurs between two pathways. Cell D. Different receptor leads to a different response.

7. Signaling Efficiency: Scaffolding Proteins and Signaling Complexes  Scaffolding proteins are large relay proteins to which other relay proteins are attached.  Scaffolding proteins can increase the signal transduction efficiency by grouping together different proteins involved in the same pathway.  In some cases, scaffolding proteins may also help activate some of the relay proteins.

8. Termination of the Signal  For a cell of a multicellular organism to remain capable of responding to incoming signals, each molecular change in its signaling pathways must last only a short time.  Signal concentration must rise and fall.  If a signaling pathway component becomes locked into one state, consequences can be dire.  The ability of a cell to receive new signals depends on the reversibility of the changes produced by prior signals.  The cellular response only occurs when the concentration of receptors with bound signaling molecules is above a certain threshold.  When the number of active receptors falls below that threshold, the cellular response ceases.  Relay molecules return to inactive form:  The GTPase activity intrinsic to a G protein hydrolyzes its bound GTP.  Phosphodiesterase converts cAMP to AMP.  Phophatases inactivate phosphorylated kinases and other proteins.