1. Cell communication Chapter 9 Genes and Development

2. Fig. 9.1 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. CytoplasmExternal environment Membrane receptor Intracellular receptor Plasma membrane Signal transduction pathway Signal transduction pathway Cellular response Cellular response Hydrophobic ligand Hydrophilic ligand

3. Fig. 9.2a Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. a. Direct Contact Adjacent plasma membrane Plasma membrane Adjacent plasma membrane Plasma membrane

4. Fig. 9.2b Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. b. Paracrine Signaling Secretory cell Adjacent target cells

5. Fig. 9.2c Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. c. Endocrine Signaling Blood vessel Distant target cells Hormone secretion into blood by endocrine gland

6. Fig. 9.2d Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. d. Synaptic Signaling Nerve cell Neurotransmitter Synaptic gap Target cell

7. Fig. 9.2 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. a.b.c.d. Synaptic SignalingEndocrine SignalingParacrine Signaling Nerve cell Neurotransmitter Synaptic gap Target cell Blood vessel Distant target cells Secretory cell Direct Contact Adjacent plasma membrane Plasma membrane Adjacent target cells Hormone secretion into blood by endocrine gland Adjacent plasma membrane Plasma membrane

8. Fig. 9.3 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Kinase Phosphatase Kinase Phosphatase O P O–O– OO–O– O P O–O– OO–O– OH Tyr ADP PiPi ATP Ser or Thr Ser or Thr Tyr PiPi

9. Fig. 9.4a Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. a. Ions Ligand (signal)

10. Fig. 9.4b Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. b. Ligand (signal) Inactive Active Cellular response

11. Fig. 9.4c Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. c.        GDP GTP Ions G protein EnzymeIon channel GPCR G protein activates either enzyme or ion channel Ligand (signal)       

13. Fig. 9.4 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. a. c. b. Ions Ligand (signal) Inactive Active        GDP GTP Ions G protein EnzymeIon channel GPCR G protein activates either enzyme or ion channel Ligand (signal) Cellular response Ligand (signal)       

14. Fig. 9.5 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Hormone Inhibitor 1. Hormones cross plasma membrane and bind to cytoplasmic receptors. 2. Hormone binding alters receptor conformation so it no longer binds inhibitor. 5. Cellular response is a change in gene expression. 3. Hormone–receptor complex translocates to nucleus. 4. Hormone–receptor complex binds to DNA. This usually turns on transcription, but can also turn it off. Signal molecule- binding domain DNA-binding site exposed DNA-binding site blocked Transcription-activating domain Gene transcription

15. Fig. 9.6 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Ligands Phosphorylated protein Intracellular kinase domain Extracellular ligand-binding domain P P P P P P P P P P P P P P P P P P Phosphate groups Transmembrane RTK proteins 1. Ligand binds to the receptor. 2. Two receptors associate (dimerize) and phosphorylate each other (autophosphorylation). 3. Response proteins bind to phospho- tyrosine on receptor. Receptor can phosphorylate other response proteins. Dimerization and autophosphorylation Cellular response

16. Fig. 9.7 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Glycogen Glycogen synthase Glycogen synthase Insulin receptor Disulfide bridge Insulin Glucose   P P P P P 1. Insulin binds to the extracellular domain of the  -subunit of the insulin receptor. 2. The  -subunit of one insulin receptor phosphorylates the other, allowing the insulin response proteins to be activated. 3. Phosphorylated insulin response proteins activate glycogen synthase. 4. Glycogen synthase converts glucose into glycogen. Insulin response protein Glycogen synthase Insulin    

17. Fig. 9.8a Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Response Signal Receptor Activator Active Inactive Active MKK MK MKKK a. Ras P P P P P P MAP kinase cascade First kinase Second kinase MAP kinase Response proteins Cellular response Response proteins Response proteins MKKK MKK MK MKKK MKK MK

18. Fig. 9.10 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Ras GT 1. Proteins bound to receptor activate Ras by exchanging GDP for GTP. 2. Ras activates the first kinase (Raf) 3. Raf activates the second kinase (MEK) 4. MEK activates MA P kinases (ERK) 5. MAP kinase (ERK) activates proteins to produce cellular responses, including transcription factors that alter gene expression Activates transcription factors Nuclear membrane Cellular response Activates transcription factors GDP Ras Raf MEK P P P P P P P P P P P P P P P Response protein Response protein Response protein Response protein Response protein Response protein P MEK ERK

19. Fig. 9.11 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. GPCR Ligand GPCR          GDP Inactive G protein GTP GDP Cellular response Effector protein GTP          Active G protein PiPi

20. Fig. 9.12 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. P –O–O –O–O O O P –O–O –O–O O O POCH 2 O O a. b. Extracellular space Cytoplasm Phospholipase C PIP 2 O C O C O CC O C O P O O –O–O P O OO–O– O–O– P O–O– OO–O– O OH DAG + IP 3 O C O C O CC O C OH P O O O O–O– P O OO–O– O–O– P O–O– OO–O– O P –O–O OO O O CH 2 DAG IP 3 P O–O– –O–OO O P O–O– O–O– O PP i cAMP Adenylyl cyclase NH 2 N N ATPcAMP + PP i Plasma membrane Cleaved by phospholipase C

21. Fig. 9.13 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Ligand GPCR GDPGTP ATP Activates PKA Cellular response Response protein Response protein Adenylyl cyclase Cytoplasm Nucleus cAMP        

22. Fig. 9.15 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Ca 2+ ER Cytoplasm Phospholipase C GPCR DAG PIP IP 3      Cellular response Ca 2+ binding protein      Ligand GDP GTP

23. Fig. 9.16 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Ca 2+ Calmodulin a.b. Active protein Inactive protein Ca 2+

24. Fig. 9.17 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. P Cytoplasm Epinephrine Glucagon PPP PPPP Glycogen CH 2 GD P P GPCR PKA cAMP Glucose-6-phosphate Adenylyl cyclase Adenylyl cyclase Phosphorylase kinase Glycogen phosphorylase GTP P ATP