1. www.ux1.eiu.edu/~cfgab

2. …and powerpoint files www.ux1.eiu.edu/~cfgab Lectures saved as Html files.. Click on “Part I-Overview“

3. If you have Microsoft Powerpoint: -You can print out the lectures 6 slides /page To print- 1. Select File- Print 2. In the pop-up window, select… Slides Handouts Pure black and white “6” slides per page OK

4. 25,000 genes 320 cell types 700 Liver-specific genes Signal transduction- ~4000 genes (16 % of genome) Receptors- 1540 (5%) Kinases- 868 (2.8%) Other components- 968 (3.2%) Signaling molecules 376(1.2%)

5. Chapter 15- Cell Communication Part I- General signaling strategies Part II- G protein signaling Part III- Enzyme-linked cell surface receptors Part IV- Proteolysis-dependent signaling pathways

6. Outline A. Two cell types Part I- General signaling strategies B. A typical signaling pathway C. Most signaling molecules are hydrophilic (water loving) D. Some signaling molecules are hydrophobic (water hating) E. A review of membranes (from chapter 10) F. Signaling over short or long distances G. Autocrine signaling H. Cells respond to specific combinations of factors I. Signaling through gap junctions J. Different cells respond differently to the same signal molecules K. Nuclear receptors are ligand-activated gene regulatory proteins L. Three classes of cell-surface receptors M. Common features of G protein-linked and enzyme- linked receptors

7. Chapter 15- Cell Communication 1. Signaling cell A. Two cell types Release Proteins ___________ Amino acids _____________ Dissolved gases (CO, NO) 2. Target cell Most secreted by ___________ or _________ These are termed ________ Respond by means of ___________ Part I- General signaling strategies

8. Ion channel-linked No details shown G-protein-linked Enzyme-linked Gq Go G proteins PKC Gs Golf PKA CREB Gene P Adenylyl cyclase cAMPAMP PIP DAG IP3 Ca++ from ER MAP-kinase (ERK) Ras Raf (a MAPKKK) MAPKK (e.g.MEK) NFkB Gene IkB/NFkB Elk-1 Gene P Grb2 GNRPs (e.g. Sos) Jak Gene TGF-  PDGF, EGF, IF ,and  IL-2,IL-3, IL-4, IL-6 Gene Nucleus Cytoplasm Elk-1jun JNK Fos jun AP1 Fos jun AP1 Cell surface receptor pathways BLA512 1/5/98 update JNK MEKK (a MAPKKK) JNKK TNF  TRADD FADD TRAF Cell death IkB/NFkB PLC  STAT NIK IKK Smad STAT Smad PLC  Caspases MAPKKK p38

9. CD14 LPS LPB TLR-4 LPS-mediated apoptosis: Which pathway is defective? NF-  B NF-kB-responsive genes NIK IKK PDTC IkB Proteasome SN50 A1, A20,,Fas, FasL,TNF, Bcl2, TRAF1,2, c-IAP1,2 IL1R1 MyD88 IRAK TAK1 TRAF6 MEKK1, 2, 3 PKC p105 p65 TPL-2 ROS FADD Caspase 8 ALLN, HMA Apoptosis P38 MAPK Calyculin A, Okadaic Acid Sorb. P38 MAPK JNKK JNK c-jun P105 phos, degraded FasR FasL FADD Caspase 8 TNF TNFR TRADD RIP TRAF2 TGFBR TNF EGFR MEK ERK1,2 PD098059

10. B. A typical signaling pathway Part I- General signaling strategies

11. C. Most signaling molecules are __________ (water loving) Thus, cannot cross plasma membrane D. Some signaling molecules are ______________ (water hating) These may move easily through the plasma membrane Part I- General signaling strategies

12. E. A review of membranes (from chapter 10) 1. A typical membrane- a __________________ with embedded __________________ Part I- General signaling strategies

13. ________ head ____________ tail 2. A membrane phospholipid Composed of fatty acids E. A review of membranes (from chapter 10) Part I- General signaling strategies

14. 3. Membranes are composed of four major _____________ Part I- General signaling strategies

15. F. Signaling over short or long distances 1. __________________2. _____________________ Requires _________ contact a. Paracrine- act locally Fast-acting, _________, high concentration Part I- General signaling strategies

16. 2. Contact independent (continued) b. ___________c. _____________ Fast acting, ____________ Slow, _______________, low concentrations e.g. hormones Part I- General signaling strategies

17. G. __________ signaling Cell secretes signal molecules that bind back to own _______ Function- _________ decisions made by a group of cells. Part I- General signaling strategies

18. H. Signaling through ____________ Small molecules are shared through these ports Ca++, cAMP can pass, but not proteins or nucleic acids I. Cells respond to specific ____________ of factors Part I- General signaling strategies

19. J. Different cells respond differently to the _______ signal molecules Example- acetylcholine Part I- General signaling strategies

20. K. Nuclear receptors are _______________ gene regulatory proteins b. Examples of signaling molecules that bind _________ receptors ____________________- derived from cholesterol; produced in adrenal, ovary, testis ________________- increase cell metabolism ______________ - from vitamin A; impt. in development _________ (UV synthesizes); Regulates Ca++ metabolism a. All are small, _________molecules carried by _________proteins 1. Ligands include Part I- General signaling strategies

21. K. Nuclear receptors are ligand-activated gene regulatory proteins c. Nuclear Receptors- belong to ______________ receptor superfamily d. All have three domains: 1. ____________________ domain Interacts with ____________ Part I- General signaling strategies 2. ___________________ domain 3. __________________ domain

22. e. Steroid hormones exhibit two response phases 1. _______ response _________ response genes activated K. Nuclear receptors are ligand-activated gene regulatory proteins Part I- General signaling strategies

23. e. Steroid hormones exhibit two response phases 2. ________ secondary response a. Primary response genes are ________ _______ b. Secondary response genes _______ _____ K. Nuclear receptors are ligand-activated gene regulatory proteins Part I- General signaling strategies

24. L. Three classes of cell-surface receptors 1. _____________-linked - (Transmitter gated ion channel) Example- ______________ 2. __________-linked – Acts through a ________________________ _______________(G protein) All are ______ transmembrane proteins Part I- General signaling strategies

25. L. Three classes of cell-surface receptors 3. ___________-linked Includes __________________ Most are ____________ transmembrane proteins Part I- General signaling strategies

26. M. Common features of G protein-linked and enzyme-linked receptors 1. Both become active via ________________ 2. Both use phosphorylation ______________ 3. Phosphorylation occurs at _______, _____or ________residues 4. ___% of mammalian genes encode these enzymes 5. Many are “__________________”

27. M. Common features of G protein-linked and enzyme-linked receptors 6. These signaling complexes can either be on a ________________...

28. M. Common features of G protein-linked and enzyme-linked receptors …. Or ________________once the receptor is activated.

29. 7. Cells can respond ___________…. ….or _________ to increasing signal molecules Conc. of effector molecules % max. activation M. Common features of G protein-linked and enzyme-linked receptors

30. The response remains after the signal disappears Example- Muscle cell determination- Turn on muscle-specific genes that regulate their own expression How? 1. The ________ activates the receptor M. Common features of G protein-linked and enzyme-linked receptors 8. Cellular memory 2. Activate a ___________________

31. 9. Cells can also become ______________ to the signal How? Ligand binding cause ____________ of receptor Receptor ______________ ______________ protein inactivated ______________ protein produced Part I- General signaling strategies