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![Gs vs Gi vs Gq
Gs and Gi coupled to adenylate cyclase [cAMP]
G q coupled to phospholipase C [Ca2+]](https://image.slidesharecdn.com/signaltransduction-140330125824-phpapp01/75/Signal-transduction-30-2048.jpg)
![IP3 + R→open of Ca2＋
channel →[Ca2＋]↑ from ER
[Ca 2+]i 0.01-1 mol/L（10-7 mol/L ）
[Ca 2+]o 2.5mmol/L（10-3 mol/L ）
5000~10000×
Ca2＋
DG PKC ↑](https://image.slidesharecdn.com/signaltransduction-140330125824-phpapp01/75/Signal-transduction-55-2048.jpg)
Uploaded byDr.M.Prasad Naidu
Signal transduction
Cellular signal transduction involves signaling molecules activating receptors on target cells to initiate intracellular responses. There are various types of signaling molecules including proteins/peptides, amino acid/fatty acid derivatives, and steroids. These molecules bind to membrane receptors and induce intracellular second messengers like cAMP, IP3, Ca2+ that activate pathways culminating in altered gene expression, metabolism, or other biological effects. The document provides details on different receptor types, intracellular signaling pathways, and examples of signaling molecules that activate them.
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Signal transduction
- 1. Cellular Signal Transduction M.PrasadNaidu MSc Medical Biochemistry, Ph.D.Research Scholar
- 2. Monad——responds directly. Multicellular organisms——signal throughelaborate system of intercellular or intracellular communication，and consequently regulate functions of organisms.
- 3. Signaling molecule Receptor oftarget cell Intracellular molecule biological effect Signal transduction
- 4. • Signaling molecules,which are released by signal-producing cells, reach and transfer biological signals to their target cells to initiate specific cellular responses.
- 5. protein & peptides:Hormone, cytokine AA & its derivatives: Gly, Glu, adrenaline, thyro xine Steroid: Sex Hormone, glucocorticosteroid Fatty acid derivatives: prostaglandin
- 6. • Secreted bycommon cells. • Reach neighboring target cells by passive diffusion. • Time of action is short. • Such as GF, PG
- 7. • Secreted byendocrine cells. • Reach target cells by blood circulation. • Time of action is long. • Such as insulin, thyroxine, adrenalin
- 8. • Secreted byneuronal cells. • Reach another neuron by synaptic gap. • Time of action is short. • Such as Acetylcholine (Ach), noradrenaline
- 9. • Simple structure,half life is short and active in chemistry . • Such as NO, CO.
- 10. • Act backto their own cells. • Such as GF, cytokine, interferon, interleukin.
- 11.
- 12. • Ca2+ ions •DG, ceramide lipid derivatives • IP3 carbohydrate derivatives • cAMP cGMP nucleotides • Ras, JAK, Raf proteins
- 13. Small molecules synthesizedin cells in response to an external signal are the second messengers, which are responsible for intracellular signal transduction. Such as Ca2+, DG, Cer, IP3, cAMP, cGMP
- 14. Third messengers arethe molecules which transmit message from outside to inside of nucleous or from inside to outside of nucleous, also called DNA binding protein.
- 15. Receptors are specificmembrane proteins, which are able to recognize and bind to corresponding ligand molecules, become activated, and transduce signal to next signaling molecules. Glycoprotein or Lipoprotein
- 16. ligand A small moleculethat binds specifically to a larger one; for example, a hormone is the ligand for its specific protein receptor.
- 17. (1) Ligand-gate ionchannels type (cyclic receptor) ligand→receptor→ion channel open or close
- 20.
- 21.
- 22. • G proteinrefers to any protein which binds to GDP or GTP and act as signal transduction. • G proteins consist of three different subunits (, , -subunit). • -subunit carries GTPase activity, binding and hydrolysis of GTP.
- 23. G protein CoupledReceptors • The human genome encodes more than 1000 Gprotein Coupled Receptors (GPCR), that transduce messages as diverse as light, smells, taste, and hormones • An example is the beta-adrenergic receptor, that mediates the effects of epinephrine on many tissues:…
- 26. Gs→ s→AC→cAMP↑ Gi→ i→AC→cAMP↓ Gq→q →PI-PLC→IP3+DAG Go→ o→ion channel Gt→ t →cGMP PDE→cGMP→ Rhodopsin
- 30. Gs vs Givs Gq Gs and Gi coupled to adenylate cyclase [cAMP] G q coupled to phospholipase C [Ca2+]
- 31. Gs vs. Gi Regulationof Adenylate Cyclase Activity Gs stimulates adenylate cyclase Gi inhibits adenylate cyclase e.g. epinephrine can increase or decrease intracellular cAMP concentrations, depending upon the receptor to which it binds adrenergic receptors couple to Gs, whereas 2 adrenergic receptors couple to Gi
- 32. Glucagon -adrenaline →s →AC↑ ACTH -adrenaline angiotensinⅡ acetylcholine(M2 M4) GF release inhibitory factor →i→AC↓
- 33. Inhibition of Gsand Gi by Bacterial Toxins Cholera toxin effects on Gs: ADP ribosylation of an Arg residue in the s subunit of Gs inhibition of associated GTPase activity Pertussis toxin effects on Gi: ADP ribosylation of a Cys residue in the i subunit of Gi an inability to inhibit adenylate cyclase activity. Thus, both toxins cause increased intracellular cAMP concentrations! © 2000 by W. H. Freeman and Company. All rights reserved.
- 34. • Tyrosine proteinkinase Receptor (catalytic receptor) IGF－R, EGF－R • Non tyrosine protein kinase Receptor Growth Hormone R, interferon R
- 37.
- 38. Membrane receptor –ANP Solublereceptor – NO, CO (4) Guanylate cyclase (GC) receptor
- 39. Intracellular R istrans-acting element cis-acting element gene expression Localized in the cytosol and/or in the nucleus. ligand: Steroid H, Vit D3, Thyroxine
- 42. • Phosphorylation or dephosphorylationof R • Phospholipid of membrane • Enzyme catalyzed hydrolysis • G protein regulation
- 43. (1) Recognize thespecial ligand (2) Binding to special ligand (3) Signal transduction biological effect
- 44. • cAMP dependent-proteinkinase A pathway • cGMP dependent PKG pathway • Ca2+ dependent PK pathway • • Tyrosine protein Kinase pathway • NF-κB pathway
- 45. H R G protein Phosphorylationof Es or functional proteins Biological effects PKA cAMPAC
- 46. ATP Mg2+ PPi cAMP H2O Mg2+ 5'-AMP AC PDE AC：Adenylate cyclase PDE： Phosphodiesterase
- 47. PDE H2O N N N N NH2 O H OHOH CH2 H H H OPO O O PO O O P O O O ATP ACPPi N NN N NH2 O H OHO CH2 H H H O PO O cAMP N N N N NH2 O H OHOH CH2 H H H OPO O O 5'-AMP
- 49.
- 50. Phosphorylate specifically Ser/Thr residuesin several proteins （1）Regulation of metabolism （2）Regulation of gene expression
- 51. hormons: glucagon, epinephrine inactiveACactive AC ATP cAMP inactive PKA active PKA phosphorylase b kinase phosphorylase b kinase P ATP ADP H2O Pi phosphorylase b P P ATP ADP Pi H2O ATP ADP glycogen synthase glycogen synthase P H2OPi protein phosphatase-1 (active) (inactive) inhibitor-1 (active) inhibitor-1 (inactive) phosphorylase a ATP
- 53. (1) Ca2+ -DAG-dependent PKC pathway H R PIP2 G protein PLC IP3 DG ER PKC Ca2+ Biological effects Phosphorylation of Es or functional proteins
- 55. IP3 + R→openof Ca2＋ channel →[Ca2＋]↑ from ER [Ca 2+]i 0.01-1 mol/L（10-7 mol/L ） [Ca 2+]o 2.5mmol/L（10-3 mol/L ） 5000~10000× Ca2＋ DG PKC ↑
- 57. • regulation ofmetabolism PKC →Ser/Thr-P of R, enzyme, Protein of Mb. • Gene expression
- 59. H R Gprotein PLC IP3 Ca2+ CaM CaMK Biological effects Phosphorylation of Es or functional proteins
- 60. Ca2＋ binding protein 4Ca2＋+ CaM → Ca2＋- CaM ↓ CaM kinase↑ ↓ Ser/Thr - P ↓ Ca2＋ pump, AC ↑ GC ↑ Es (glycogen synthase, phosphorylase kinase)
- 62. Biological effects Phosphorylation ofEs or functional proteins ANP NO, CO Soluble GC PKG cGMP Receptor- linked GC
- 63. (2) Function ofPKG Ser/Thr- P of protein and E Mg2+ PPi H2O Mg2+ GTP cGMP 5'-GMP GC PDE GC: Guanylate cyclase
- 64. ANP（atrial natriuretic peptides） ↓ GCNO ↓ cGMP ↓ PKG ↓ Vascular dilatation
- 65. cis-actingelement nucleus expression cell memberane phosphorylationof enzymesor proteins effects CaM-PK Ca2+ -CaMCa2+ IP3 DGcAMP cGMP PKA PKG PKC ATP GTP PIP2(PC) GAC GC GPL peptide hormones neurotransmitters AFP neurotransmitters hypothalamic pituitrin Ptrans-actingfactor
- 66. • TPK receptoris related to proliferation, differentiation, dissociation, carcinomatous change. • TPK： receptor TPK：Membrane. non receptor TPK：cytosol
- 67. • GRB2, SOS,Ras, Raf • Small G protein: Ras • MAPK (mitogen-activated protein kinase)： MAPK、MAPKK、MAPKKK • MAPKs belong to a family of serine/threonine kinases (kinases add phosphate groups to/phosphorylate other proteins) • They participate in cell growth, differentiation, transformation, apoptosis (controlled cell death) and others
- 69. ÊÜÌåÐÍTPK ϸ °û Ä EGF, PDGF receptor TPKRas－GTP SOS－P GRB2－P Raf－P MAPKK－P MAPK－P trans-acting factor expression nucleus －P
- 70. (2) JAKs－STATpathway • JAKs(JANUS KINASES) • STAT: Signal transductors and activator of transcription
- 71. ÖÊĤ ¸ÉÈÅËØÓ¦´ðÔª¼þ ºËĤ »ùÒò £- PP£- JAK 113 91 84 48 113 P 91P 84P 48 113 91 84P P P interferons & GH inactive STAT Plasma membrane STAT complex Nuclear membrane gene Interferons response element transcription
- 73. • Steroid H,VD3, Thyroxine • Cytosolic R: glycocorticosteroid H • Nuclear R: thyroxine, estrogen, androgen, progesterone
- 75. Effect by membrane receptors Effect by intracellular receptors Intracellular molecules Extracellular molecules Signal molecules cAMP,cGMP, IP3, DG, Ca2+ Proteins and peptides: Hormones, cytokines Amino acid derivatives: Catecholamines Fatty acid derivatives: Prostaglandins Steroid hormones, Thyroxine, VD3