1. Cell Communication Chapter 7

2. 7.1 Cell Communication: An Overview  Cells communicate with one another through Direct channels of communication Specific contact between cells Intercellular chemical messengers

3. Apoptosis Fig. 7-1, p. 140

4. Intercellular Chemical Messengers  Controlling cell Releases signal molecule that causes response of target cells  Target cell processes signal in 3 steps: Reception, transduction, response  Signal transduction Series of events from reception to response

5. Signal Transduction Fig. 7-2, p. 142

6. Reception

7. 7.2 Cell Communication Systems with Surface Receptors  Peptide hormones and neurotransmitters Primary extracellular signal molecules recognized by surface receptors in animals  Surface receptors Integral membrane glycoproteins  Signaling molecule Bound by a surface receptor Triggers response pathways within the cell

8. Surface Receptors  Cell communication systems based on surface receptors have 3 components: (1) Extracellular signal molecules (2) Surface receptors that receive signals (3) Internal response pathways triggered when receptors bind a signal

9. Peptide Hormones  Peptide hormones Small proteins  Growth factors Special class of peptide hormones Affect cell growth, division, differentiation

10. Neurotransmitters  Neurotransmitters include Small peptides Individual amino acids or their derivatives Chemical substances

11. Surface Receptors  Surface receptors Integral membrane proteins Extend entirely through the plasma membrane  Binding of a signal molecule Induces molecular change in the receptor that activates its cytoplasmic end

12. Response of Surface Receptor

13. Cellular Response Pathways (1)  Cellular response pathways Operate by activating protein kinases  Protein kinases add phosphate groups Stimulate or inhibit activities of target proteins, producing cellular response

14. Cellular Response Pathways (2)  Protein phosphatases Reverse response Remove phosphate groups from target proteins  Receptors are removed by endocytosis When signal transduction is finished

15. Phosphorylation

16. Amplification  Each step of a response pathway catalyzed by an enzyme is amplified Each enzyme activates hundreds or thousands of proteins that enter next step in pathway  Amplification Allows full cellular response when few signal molecules bind to receptors

17. Amplification

18. 7.3 Surface Receptors with Built-In Protein Kinase Activity  Receptor Tyrosine Kinases

19. Receptor Tyrosine Kinases  Receptor tyrosine kinases bind signal molecule Protein kinase site becomes active Adds phosphate groups to tyrosines in the receptor itself, and to target proteins  Phosphate groups added to cytoplasmic end of receptor are recognition sites for proteins activated by binding to the receptor

20. Protein Kinase Activity

21. 7.4 G-Protein–Coupled Receptors  G proteins: Key molecular switches in second- messenger pathways  Two major G-protein–coupled receptor response pathways involve different second messengers

22. G-Protein-Coupled Receptors  G-protein-coupled receptors activate pathways Binding of the extracellular signal molecule (first messenger) activates a site on the cytoplasmic end of the receptor

23. G-Protein-Coupled Receptors Fig. 7-8, p. 147

24. G-Protein Activation  Activated receptor turns on a G protein, which acts as a molecular switch  G protein Active when bound to GTP Inactive when bound to GDP

25. Active G Protein  Active G protein Switches on the effector of the pathway (enzyme that generates second messengers)  Second messengers Small internal signal molecules Activate the protein kinases of the pathway

26. Response Pathways

27. Second Messengers: cAMP  1st of two major pathways triggered by G- protein-coupled receptors  Effector (adenylyl cyclase) generates cAMP as second messenger  cAMP activates specific protein kinases

28. cAMP Receptor-Response Pathways Fig. 7-10, p. 148

29. cAMP Fig. 7-11, p. 148

30. Second Messengers: IP 3 and DAG (1)  2nd major pathway triggered by G-protein– coupled receptors  Activated effector (phospholipase C), generates two second messengers, IP 3 and DAG

31. Second Messengers: IP 3 and DAG (2)  IP 3 activates transport proteins in the ER Releasing stored Ca 2+ into the cytoplasm  Released Ca 2+ (alone or with DAG) activates specific protein kinases Adds phosphate groups to target proteins

32. IP 3 /DAG Receptor-Response Pathways

33. Pathway Controls  cAMP and IP 3 /DAG pathways are balanced by reactions that eliminate second messengers Stopped by protein phosphatases that continually remove phosphate groups from target proteins Stopped by endocytosis of receptors and their bound extracellular signals

34. Mutations  Mutated systems can turn on the pathways permanently, contributing to progression of some forms of cancer

35. Gene Regulation: Ras  Some pathways in gene regulation link certain receptor tyrosine kinases to a specific G protein (Ras)  When the receptor binds a signal molecule, it phosphorylates itself Adapter proteins then bind, bridging to and activating Ras

36. Activated Ras  Activated Ras turns on the MAP kinase cascade  Last MAP kinase in cascade phosphorylates target proteins in the nucleus Activates them to turn on specific genes  Many of these genes control cell division

37. Gene Regulation

38. 7.5 Pathways Triggered by Internal Receptors: Steroid Hormone Receptors  Steroid hormones have widely different effects Depend on relatively small chemical differences  Response of a cell to steroid hormones Depends on internal receptors and the genes they activate

39. Steroid Hormone Receptors  Steroid hormones penetrate plasma membrane Bind to receptors within the cell  Internal receptors Regulatory proteins that turn on specific genes when activated by binding a signal molecule Produce cellular response

40. Two Domains of Steroid Hormone Receptors  Steroid hormone receptors One domain recognizes and binds a specific steroid hormone One domain interacts with the controlling regions of target genes

41. Gene Activation: Steroid Hormone Receptors

42. Cell Response  Cell response to a steroid hormone Depends on whether it has an internal receptor for the hormone  Type of response within the cell Depends on the genes that are recognized and turned on by an activated receptor

43. 7.6 Integration of Cell Communication Pathways  Cross talk

44. Cross-Talk  Cell signaling pathways communicate with one another to integrate responses to cellular signals  May result in a complex network of interactions between cell communication pathways

45. Cross-Talk

46. Modification of Cell Response  Cross-talk often results in Modifications of cellular responses controlled by the pathways Fine-tuning effects of combinations of signal molecules binding to receptors of a cell

47. Cell Communication Pathways In Animals  Inputs from other cellular response systems also can become involved in the cross-talk network Cell adhesion molecules Molecules arriving through gap junctions