Signal Transmission Flashcards

1
Q

What is cell signaling?

A

The ability of cells to receive and act on signals from their environment is fundamental to life

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2
Q

How do cells respond to signals of the environment?

A

Cells respond to signals from their environment by regulating their activities and the activities of other cells

Regulation of cellular processes involve regulation of metabolism and gene expression

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3
Q

What is metabolic regulation?

A

Is the balanced of the production of energy and synthesis of end products to the metabolic demands of the cell

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4
Q

What is the importance of metabolic regulation?

A
  • It ensures a constant supply of energy and is critical to survival in a changing environment
  • An effective communication system is needed to coordinate the metabolic activities of cells
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5
Q

Metabolic regulation depends on signals inform the cells, what 2 ways can this be done?

A

A. Intracellular (signals originate within cells)

B. Intercellular (between cells)

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6
Q

Most cells are ____________ in nature

A

Chemical

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7
Q

Give a brief summary of intracellular signals

A
  • Signaling via secreted molecules. Most important route for metabolism
  • Signaling via cell surface molecules
  • Signaling via gap junctions
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8
Q

Give an overview of signal transduction

A
  1. Synthesis and release of signaling molecule (first signal) in response to a stimulus
  2. The signaling molecule is transported to target cell where it binds to a receptor protein
  3. Activated receptor generates intracellular signals that result in an appropriate response
  4. Termination of response
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9
Q

What is the function of receptors in signal transduction ?

A

They bind to extracellular signal and transmits the signal into the cell by promoting activation or synthesis of intracellular molecules

These then lead to target proteins and a cellular proteins

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10
Q

List the general features of signaling transduction

A
  • Specificity
  • Amplification
  • Desensitization/adaptation
  • Integration
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11
Q

Describe the specificity of signaling transduction.

A

Signal molecule fits binding site on its complementary receptor; other signals do not fit

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12
Q

Describe the amplification of signal transduction

A

When enzymes activate enzymes, the number of affected molecules increases geometrically in an enzyme cascade

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13
Q

Describe the desensitization/adaptation of signal transduction

A

Receptor activation triggers a feedback circuit that shuts off the receptor or removes it from the cell surface

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14
Q

Describe integration of signal transduction

A

When two signals have opposite effects on a metabolic characteristic such as the concentration of a second messenger X, or the membrane potential Vm, the regulatory outcome results from the integrated input from both receptors

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15
Q

How do intracellular receptors work?

A
  • Cytoplasmic receptor can bind to the signal molecule(ligand) then translocations to the nucleus
  • Or receptor can be found in the nucleus bound to the DNA or proteins.
  • Usually bind to steroid hormones or other lipophilic signal molecules(thyroid hormone)
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16
Q

What are the types of signal transduction pathways?

A
  1. Steroid receptor
  2. Gated ion channel
  3. Enzyme receptor(catalytic)
  4. G-protein coupled receptor(GCPR)
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17
Q

Give the general Features of steroid receptor transduction pathways

A
  • Steroid binds to receptor in cytoplasm or nucleus of cells
  • Act as ligand-activated transcription factor
  • Activated receptor binds to DNA and alters the rate of gene transcription
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18
Q

What are examples of steroid receptor

A

Androgen hormone receptor

Progesterone receptor

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19
Q

Give the general features of the Gated ion channel

A

Binding opens or closes an ion channel

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20
Q

Give examples of gated ion channel receptors

A

Nichotonic ACh receptors of muscle or nerve, y-aminobutyric acid (GABA), Glycine receptors in the CNS

21
Q

Give the general features of enzyme receptor (catalytic)

A

Catalyzes production of a intra-signaling molecule

22
Q

Give an example of an enzyme receptor (catalytic)

A

Tyrosine kinase receptor

23
Q

Give the general features of G-protein Coupled receptor(GPCR)

A

G-proteins activate enzymes that produce second messengers

24
Q

Give an example of G-protein Coupled Receptor(GPCR)

A

Epinephrine/Norepinephrine receptor(beta and alpha adrenergic)

25
Q

How long does steroid receptor mechanism takes?

A

May take hours or days(slow)

26
Q

Explain the steroid mechanism of transduction

A
  1. Hormone(H), carried to the target tissue on serum binding proteins diffuses across the plasma membrane and binds to its specific receptor protein (Rec) in the nucleus
  2. Hormone binding changes the conformation of it forms homozygous or heterodimers with other hormone receptor complexes and binds to specific regulatory regions called hormone response elements (HREs) in the DNA adjacent to specific genes
  3. Binding regulated transcription of the adjacent gene(s), increasing or decreasing the rate of mRNA formation
  4. Altered levels of the hormone-related gene product produce the cellular response to the hormone
27
Q

Describe gated ion channel signal transduction

A

Receptor linked to ligand or voltage-gated ion channel

Binding of neurotransmitter causes channel to open or close

Results in rush of ions through ion channel altering membrane potential promoting or inhibiting nerve impulse transmission

28
Q

Describe enzymatic (catalytic) receptor function

A
  • Transmembrane catalytic receptors that have enzymatic activity as part of their structure
  • Enzyme is a tyrosine- specific protein kinase(adds a phosphate to specific tyrosine residues)
  • Contain an extracellular domain for binding ligand and an intracellular domain with tyrosine kinase activity
29
Q

Describe insulin receptors as enzyme (catalytic) receptors

A

Insulin receptor in which binding of ligand —> ATP cleavage, autophosphorylation and phosphorylation of specific tyrosine residues in target proteins —> signaling cascade and response activation

30
Q

What are the importance of the extracellular domain of G-coupled Protein receptors?

A

The extracellular domain contains the binding site for a ligand (a hormone or neurotransmitters)

31
Q

Describe the importance of the intracellular domains in G-coupled protein receptors

A

Intracellular domain that interacts with G-proteins

32
Q

Briefly describe GPCRs signal transduction

A
  • The hormone or neurotransmitter, is the first messenger that binds to the plasma membrane receptor
  • Receptor activates a G-protein, that stimulates an effector enzyme to produce a second messenger

Example: Adenylyl Cyclades system(cAMP)

Phosphoinositide system(IP3, DAG and Ca2+)

33
Q

What are hetero-trimeric G proteins?

A
  • Intracellular signaling proteins that can bind to and hydrolyzed GTP(guanosine triphosphate )
  • Composed of three subunits a, B and y
  • Three subunits associate and a subunit binds GDP when inactive
34
Q

How are Hetero-trimeric G proteins activated and inactivated?

A
  • Activated by ligand binding to GPCRs
  • a subunit exchanges GDP for GTP and dissociates from B and y subunits when active
  • GTPase activity hydrolyzes GTP and G-protein reverts to inactivate state
35
Q

Describe intracellular second messengers

A
  • small soluble intracellular molecules produced in response to activation of a cell surface receptor
  • they trigger a cascade of intracellular events(enzyme activation, inhibition) that activates an appropriate cellular response
36
Q

Give examples of intracellular second messengers

A
  • cAMP
  • IP3, DAG, Ca2+
  • cGMP
  • NO(nitric oxide)
37
Q

Describe the Adenylyl Cyclades System of GPCR signaling systems

A

Second messengers is cAMP

  1. Binding of hormone to receptor
  2. Activation of Gsa
  3. Gsa protein activates adenylyl Cyclase
  4. Adenylyl cyclase synthesizes cAMP from ATP
  5. cAMP activates Protein kinase A
  6. Protein kinase A phosphorylates target proteins resulting in cellular responses
  7. Phosphodiesterase hydrolysis cAMP to 5’-AMP and terminates signal
38
Q

Contrast the signal(first messenger) Adenylyl cyclase system and phosphoinositide (GPCR signaling systems)

A

Adenylyl cyclase system-Glucagon, Epinephrine/Norepinephrine

Phosphoinositide system- Epinephrine/norepinephrine

39
Q

Contrast the receptors of Adenylyl cyclase system and phosphoinositide system (GPCR)

A

Adenylyl Cyclase systems - Glucagon receptor, B-adrenergic receptor

Phosphoinositide system- A-adrenergic receptor

40
Q

Contrast the G proteins in Adenylyl Cyclase and Phosphoinositide systems

A

Adenylyl cyclase - Gs

Phosphoinositide- Gq

41
Q

Contrast the effector enzymes of Adenylyl cyclase and phosphoinositide systems (GCPR signaling )

A

Adenylyl cyclase effector enzyme - Adenylyl cyclase

Phosphoinositide effector enzyme- Phospholipase C

42
Q

Contrast second messengers between Adenylyl cyclase and phosphoinositide (GPCR systems)

A

Adenylyl cyclase- cAMP

Phosphoinositide- IP3, DAG, Ca 2+

43
Q

Contrast the Ser/Thr kinase between Adenylyl cyclase and phosphoinositide

A

Adenylyl Cyclase- protein kinase A

Phosphoinositide- Protein kinase C

44
Q

What is phosphotidylinositol 4, 5-bis-phosphate (PIP2)?

A

Phospholipid found in the inner leaflet of the plasma membrane

45
Q

What role does Phosphatiylinositol-4,5-is-phosphate (PIP2)play in the phosphoinositide system?

A
  • Phospholipase C cleaves PIP2 to generate IP3 and DAG
  • IP3 is soluble and moves through cytoplasm
  • DAG is hydrophobic and remains in the plasma membrane

(Primary messenger)

46
Q

Give the process phosphoinositide system after the second messenger

A
  • second messengers produced are IP3, DAG and Ca2+
    1. Gqa activates Phospholipase C (PLC)
    2. PLC cleaves PIP2 to IP3 and DAG
    3. IP3 causes Ca2+ release from ER
    4. DAG activates Protein kinase C
    5. Protein kinase C phosphorylates substrate proteins resulting in cellular responses
    6. Protein kinase C requires DAG, Ca2+ and phospholipids for maximal activity
47
Q

What are the sites of signal termination?

A
  • removal of signaling molecule
  • removal of receptor
  • inactivation of signal transduction events
48
Q

Give examples of signal termination

A
  • degradation of insulin by liver
  • Intrinsic GTPase activity of G-proteins
  • Hydrolysis of cAMP by phosphodiesterase
  • Reversal of phosphorylation effects by phosphatases