Fundamentals of Cell Biology

1. Fundamentals of Cell Biology Chapter 11: Signal Transduction and Cellular Communication

2. Chapter Summary: The Big Picture (1) • Chapter foci: • Structure of a signaling pathway • Types of signals cells detect and the role of the receptor • Molecules most commonly found in signaling pathways • Examples of well known signaling pathways examined in order to understand all of the aforementioned

3. Chapter Summary: The Big Picture (2) • Section topics: • Signaling molecules form communication networks • Cell-signaling molecules transmit information between cells • Intracellular signaling proteins propagate signals within a cell • A brief look at some common signaling pathways

4. Signaling molecules form communication networks • Key Concepts: • Signaling networks relay information from the extracellular environment to the interior of a cell. • The basic unit of a signaling network is a signal transduction pathway, which carries one specific signal in a single direction from the source (a receptor) to the effector. • Most signal transduction pathways are comprised of several different molecules that activate each other in a carefully controlled sequence of binding interactions. • .

5. Signal Transduction Pathway • function: convert extracellular information into an appropriate cellular response • composed of: • signals • receptors • signaling proteins • second messenger molecules Figure 11.01: Simple schematic of signal transduction pathways.

6. Signal Transduction Pathway Figure 11.02: Signaling pathways use linear, convergent, divergent, and branched signaling pathways to generate complex responses to external signals.

7. Signaling networks are long and complex

8. Cell-signaling molecules transmit information between cells • Key Concepts: • Signals arise from the extracellular space, and must bind a receptor to be effective. • Most signals are molecules that cannot penetrate the plasma membrane, so they bind to receptor proteins on the cell surface. Those signals can then pass through membranes and are bound by receptors in the cytosol. • Receptors are grouped into six classes, according to their structure, binding partners, and cellular location.

9. Signaling begins when ligand binds to target receptor • Types of ligands: • Membrane impermeable • neurotransmitters • Membrane permeable • estrogen, testosterone • Physical signals • pressure, temperature, light

10. 6 classes of receptors detect a vast array of environmental stimuli Figure 11.03: Receptors are grouped into six classes based on their structure and cellular location.

11. G-protein coupled receptors activate G proteins Figure 11.04: The general structure of a seven transmembrane receptor.

12. Receptor protein kinasesphosphorylate signaling proteins Figure 11.05: Model of growth factor receptor activation.

13. Receptor protein kinasesphosphorylate signaling proteins Figure 11.06: Serine/threonine kinase receptor activation leads to phosphorylation of a signaling protein.

14. Figure 01.14C: The 20 most common amino acids are classified into three classes based on the structure of their side chains.

15. Phosphoprotein phosphatases remove phosphate groups from signaling proteins Figure 11.07: Protein phosphatases break the phosphester bond linking phosphate groups to serine, threonine, and tyrosine side chains.

16. Guanylyl cyclases produce the signaling molecule cyclic GMP Figure 11.08: Receptor guanylyl cyclases are homodimeric receptors that contain a cytoplasmic domain that converts GTP into cyclic GMP.

17. Ion channel receptors permit ion fluxes Figure 11.09: Ligand-gated channels typically form a central pore that opens when a ligand binds to the receptor.

18. Transmembrane scaffolds recruit intracellular signaling proteins Figure 11.10: Integrin receptors form signaling scaffolds.

19. Nuclear receptors are transcription factors Figure 11.11: The steroid receptor binds to steroid hormones when they diffuse into the cytosol.

20. Intracellular signaling proteins propagate signals within a cell • Key Concepts: • Signaling proteins rapidly transmit and amplify signal information. • As information passes through a signal transduction pathway, it often changes physical form. • Signaling proteins are grouped into six classes based on their structure, location, and mechanism of signal transmission. • Second messengers are non-protein molecules that link signaling proteins together in signal transduction pathways.

21. G proteins are molecular switches Figure 11.12: The GTPase cycle repeats continuously, shifting the G protein between active and inactive states like a switch.

22. G proteins are molecular switches Figure 11.13: A heterotrimeric G protein signaling cycle.

23. GTPase cycle

24. Protein kinases phosphorylate downstream signaling proteins Figure 11.14: Protein kinases add phosphate groups to signaling proteins and effectors.

25. Lipid kinases phosphorylate phopsholipids Figure 11.15: Lipid kinases add phosphates to phospholipids.

26. Calcium fluxes control calcium-binding proteins Figure 11.16: Calmodulin is an example of a calcium sensitive signaling protein.

27. Adenylyl cyclases form cyclic AMP Figure 11.18: Phosphodiesterase cleaves the phosphoester bond between the phosphate and the 3' carbon of ribose, converting cAMP to AMP. Figure 11.17: Adenylyl cyclase is a target of competing regulatory pathways.

28. Adaptors facilitate binding of multiple signaling proteins

29. Signaling, an overview Ligand Gated Ion Channel Scaffold (Integrin) Guanylyl Cyclase S/TKR Steroids RTK GPCR Signaling Proteins Hetero-trimeric G Proteins Mono-meric G Proteins Protein Kinases Calcium Binding Proteins Lipid Kinases Adenylyl Cyclases AdaptorProteins Second Messengers Steroid Receptors Lipids +Hydrocarbons Nucleotides Ions

30. iClicker Time What causes the α and βγ subunits of heterotrimeric G proteins to dissociate from each other? a. Phosphorylation of the α subunit b. Phosphorylation of the G protein-linked receptor c. Phosphorylation of GEF d. A change in shape in G protein linked receptors e. Cleavage of GTP to GDP by the α subunit.

31. A brief look at some common signaling pathways • Key Concepts: • Hundreds of different receptors, signaling proteins, and effectors combine into a complex network of interacting pathways within a single cell. • Despite the tremendous complexity of signaling networks, many share common features that help set the standard for our current understanding of how signal transduction pathways function. • Some signal transduction pathways trigger short-term cellular changes via very long and complex sets of signaling interaction, while others contain very few steps and have relatively long-term effects on cells.

32. Protein tyrosine kinase signaling pathways control cell growth and migration Figure 11.19: A simplified version of an FGF signaling pathway.

33. Heterotrimeric G protein signaling pathways regulate a great variety of cellular behaviors Figure 11.20: A sample cAMP signaling pathway.

34. Phospholipid kinase pathways work in cooperation with protein kinase and G protein pathways Figure 11.21: The phosphoinositol 4,5-bis phosphate (PIP2) signaling pathway.

35. Phospholipid kinase pathways work in cooperation with protein kinase and G protein pathways Figure 11.22: PIP2 phosphodiesterase and IP3 phosphatase inhibit PIP2 signaling.