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Chapter 16

Chapter 16. Cellular signal transduction. A general introduction. When outer environment changes ：. Unicellular organism —— Directly responds to extraneous signals. Multicellular ——

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Chapter 16

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  1. Chapter 16 Cellular signal transduction

  2. A general introduction

  3. When outer environment changes： Unicellular organism —— Directly responds to extraneous signals. Multicellular —— transmits the information by the intercellular complicated signal transduction system, and regulates the activity of body.

  4. Intercellular signal transduction can be transduced by： * directly contact between adjacent cells. * Regulation of metabolism and function of itself and other cells by means of secreting chemical substances by cells. chemical substances which regulate the life activity of cells ——signaling substance

  5. stimulation General manner of intercellular signal transduction : target cell secretive cell target cell

  6. second messengers signal substance (first messenger) receptor effector protein effector protein

  7. section 1 signaling substances

  8. Ⅰ、 Intercellular signaling substance * Definition A general designation of chemical substances which are secreted by the cells in order to regulate the life activity of the target cells. * Chemical character protein, peptide, amino acid derivatives, steroid hormone, fatty acid derivatives, NO and so on

  9. * Classification 1、Local chemical medium Paracrine signal

  10. For instance: growth factor, NO, prostaglandins and so on. characteristics ： • Paracrine signal molecules are secreted by common cells in vivo ； • Paracrine signal molecule do not enter blood circulation, but arrive nearby target cells by diffusion. • The effective time is usually short.

  11. 2、Hormones Endocrine signal

  12. Characteristics： • endocrine signal molecule are secreted by endocrine cells which are specially differentiated; • arrive the target cells through the blood circulation; • effective time of most of them is longer. For instance: Insulin, thyroxine, adrenalin and so on.

  13. 3. Neural transmitter Characteristic ： • synapse-secreted signal; • secreted by nerve cell; • arrive to the target cell through the synaptic cleft ； • effective time is short. e.g. acetylcholine、noradrenaline and so on .

  14. Others ： Some intercellular signaling substances can act on the same cell or on the secreting cells themselves. They are called autocrine signal. Some intercellular signaling substances can transmit information in different bodies, e.g. Insect sex hormone.

  15. the pathways of intercellular signaling substances affect the cellular functions

  16. Ⅱ、Intracellular signaling substance * DefinitionChemical substance which is transmiting cell regulation signals within the cells . * Chemical property: Inorganic ions： Ca2+ Derivative of lipid ：DAG、Cer Derivative of saccharide: IP3 nucleotide：cAMP、cGMP signal protein molecule

  17. ※ Secondary messenger Small molecules which are used to transduce information within the cells. For instances： Ca2+、DAG、IP3、Cer、cAMP、cGMP and so on .

  18. Section 2 receptor

  19. ※Receptor Receptors are proteins, anchored in cell membrane or in the cells, which can recognize and bind with specific biological active molecules, and result in biological effect. ※ Ligand biological active molecules which can bind with receptor are named as ligand.

  20. Intracellular receptor The receptors located in the cytosol and nucleus are all DNA binding proteins. Membrane receptor Large number of the receptors located on the plasma membrane are enchasing glycoprotein 。

  21. Ⅰ.Classification, structure and function of receptors 1. Membrane receptor • circular receptor——the ion channel • dependent on the ligand Acetylcholine receptor

  22. G protein couple region B. -helix receptor with seven transmembrane fragments —serpentine receptor

  23. ※ GTP/GDP binding protein （G protein） G protein, which is combined with GTP or GDP, is a kind of peripheric protein which is located on the cytosolic face of the plasma membrane. It is composed of three subunits: 、、. G protein has two conformations：inactive state; active state.

  24. Inactive Active G protein cycle

  25. Signal transduction mediated by this receptor can be reduced to： hormone receptor G protein enzyme second messenger Protein kinase Enzyme or other functional protein biological effect

  26. G proteins in the process of the signal transduction AC: adenylate cyclase PLC: phospholipase C

  27. C． -helix receptor with single transmembrane fragment： IgG-linked sequence membrane TPK EGF-R IgG: immunoglobulins

  28. Tyrosine protein kinase-linked receptor： Receptor has the activity of tyrosine protein kinase after binding with ligand. For instance: insulin receptor IGF-R epithelium growth factor EGF-R） Receptor not linked with tyrosine protein kinase： Receptor is linked with tyrosine protein kinase after binding with ligand so to produce the activity of TPK. For instance: growth hormone receptor, interferon receptor.

  29. Autophosphorylation： Some receptors with a single transmembrane fragment have the activity of catalysis. When they bind with ligand, they will form a receptor-dimer. The TPK in each monomer will be activated, and phosphorylate their counterpart in dimer. This process is known as autophosphorylatoin.

  30. Acting mechanism of EGF:

  31. 2. Intracellular receptor A． Structure of receptor ＮＨ2 COOH Highly variable domain DNA binding domain hormone binding site

  32. B. Correlated ligand —— Steroid hormone, thyroxine and retinoic acid and so on C. Function —— Most of intracellular receptors are trans-acting factors. After binding to the corresponding ligands, they can bind with DNA cis-acting elements to regulate gene transcription.

  33. Ⅱ 、acting characteristic of receptor • High specificity • High affinity • Saturability • Reversibility • Specifically • acting mode

  34. Ⅲ、Regulation of the activity of receptor • Influence of phosphorylation and dephosphorylation • Influence of metabolism of membrane lipid • enzymatic hydrolysis • Regulation of Ｇprotein

  35. section 3The pathway of signal transduction

  36. Signal transduction mediaed intracellular receptor： Signal transduction mediaed membrane receptor：

  37. 1. Signal transduction mediated by membrane receptor： • The pathway of cAMP-protein kinase • The pathway of cGMP-protein kinase – The pathway of Ca2+-dependent protein kinase • the pathway of tyrosine protein kinase • the pathway of nuclear factor  

  38. A. The pathway of signal transduction mediated by cAMP-protein kinase A a、constituents： Extracellular signaling molecules（mainly are glucagon、adrenalin and adrenotrophin）. Receptor，G protein，AC，cAMP , PKA

  39. phosphodiesterase ＡＣ cAMP 5`-AMP ATP Mg2+ Mg2+ H2O PPi b．Synthesis and degradation of cAMP ：

  40. AC PPi H2O cAMP PDE AMP ATP (Adenylate cyclase, AC) (Phosphodiesterase, PDE)

  41. cAMP cAMP R R C C C C R cAMP R cAMP C．Acting mechanism of cAMP： ＋ 4cAMP ＋ • Activates of cAMP protein kinase • Ｃ：catalytic subunit Ｒ： regulation subunit

  42. （cAMP-dependent protein kinase，PKA） Serine/threonine protein kinases family R：regulation subunit C：catalytic subunit

  43. D．Effect of PKA ： （a）regulation on metabolism realize the regulation by phosphorylating the effector proteins.

  44. glycogen n+1 UDP Pi glycogen synthase phosphorylase UDPG PPi G-1-P UTP G-6-P Glu

  45. adrenalin＋receptor phosphorlatase kinase b ATP PPi PKA phosphoprotein phosphatase adrenalin · receptor complex ⊕ phosphorlatase kinase a Activating Ｇ-protein ATP phosphorylase ｂ phosphorylase ａ Activating AC  H2O PPi ATP cAMP phosphoprotein phosphatase  ⊕ inhibitorＩb PKA phosphoprotein phosphatase inhibitorＩa PPi ATP Effection of Adrenalin on the metabolism of glycogen

  46. Phosphorylation of substrate protein by PKA

  47. （b）Regulation effect on gene expression In transcription regulatory region of the genes regulated by cAMP, there is a consensus sequenc（TGACGTCA）which is known ascAMP response element (CRE). cAMP response element binding protein (CREB) can interact with CRE to regulate the transcription of the gene.

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