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Biochem > Lecture 10: Signal Transduction > Flashcards

Lecture 10: Signal Transduction Flashcards

1
Q

Transduction

A

-stepwise regulation of interactions of intracellular signaling proteins and often amplified
-info from environment transmitted inside a cell generates response

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2
Q

Eliciting of cellular response

A

-gene expression
-membrane transport
-metabolism
-cell growth/death

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3
Q

Transduction purpose

A

-coordinate cell metabolism, growth, development
-ensure homeostasis
-respond to external stimuli

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4
Q

Signal Transduction cascade

A

-sequential biochemical events to transfer a signal through a series of reactions that activate intermediate molecuels and to a final target

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5
Q

Signal cascade

A
  1. reception
  2. amplification
  3. G-protein
  4. Amplification
  5. Protein Kinase
  6. Amplification
    7.Amplification
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6
Q

Signaling cascade amplification

A

by producing multiple intracellular activated molecules for every one receptor that is bound

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7
Q

Modes of cell-cell communication

A

-juxtacrine
-endocrine
-paracrine
-synaptic/neuronal
-autocrine

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8
Q

Juxtacrine signaling

A

-cell-cell contact
-2 surface proteins bind

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9
Q

Endocrine signaling

A

-hormones secretes into bloodstream
-LOW concentration
-HIGH affinity receptor
-response is minutes to hours

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10
Q

Paracrine signaling

A

-secreted ligands target nearby cells
-HIGH local concentration
-LOW affinity receptor
-rapid response (secs to mins)

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11
Q

Synaptic/neuronal signaling

A

-synapse between neuron and target is short distance
-VERY HIGH concentration
-VERY LOW affinity receptor
-dissociate rapidly
-technically specialized PARACRINE

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12
Q

Autocrine signaling

A

-sender and target are same cell
-response time similar to paracrine (secs to mins)

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13
Q

Secreted molecules

A

-first messengers
-ligands for receptors
-vary in size/chemical type
-receptors differ from intracellular proteins to integral membrane proteins

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14
Q

Big first messengers

A

-proteins
-polypeptides

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15
Q

Small first messengers

A

aa, lipids, nucleotides

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16
Q

Chemical types of first messengers

A

-steroids, vitamins, histamine, modified amino acids

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17
Q

Intracellular receptor for steroid/thyroid hormones, vitamins

A

-hydroPHOBIC first messenger
-Lipid-soluble hormone diffuses through plasma membrane and binds receptor

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18
Q

Signal Propogation of intracellular receptor of steroid hormones

A

-by changes in receptor upon binding
-leads to altered gene expression

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19
Q

Steroid Nuclear Receptors

A

-initiate signaling processes activated by steroid hormones
-changes in gene expression over HOURs to DAYs
-bind hormone then bind to specific sites on DNA to activate transcription
-cancer

20
Q

Steroid Nuclear Receptors as TFs

A

-direct interaction with DNA and control gene expression
-key to embryonic development, and homeostasis, metabolism

21
Q

HETEROdimer Nuclear Receptor

A

-Retinoid X receptor and liver receptor bound to DNA in response element
-DBD-hinge-LBD
-2 DBDs bind DNA promoter regions
-LBD has agonist ligands and peptide from NR coactivator

22
Q

Nuclear receptors as drug target

A

-ligand inducible transduction
-drugs blocking estrogen or androgen receptor in breast and prostate cancers

23
Q

Thyroid Nuclear Receptor

A

-thyroid hormone
-lipid soluble
-diffuse through membrane
-binds receptor inside cell
-HOMOdimerization of receptor
-recruitment of coregulatory proteins
-promotes DNA binding and specific recognition of TRE
-turns on or off transcription

-green DBD on top
-purpkle LBD on bottom
-ligand bind middle of LDB

24
Q

TNR resembles heterodimer nr

A
25
Q

Integral membrane protein

A

-effector protein
-coupling protein
= activate effeector and other enzymes
-enzyme activity
=alters receptor activity
-opens ion channel
=changes membrane potential

26
Q

Second messengers

A

-sometimes
-small
-transmit and amplify initial signal from extracellular first messenger binding to receptor
-inorganic or organic products of enzyme-catalyzed reactions

27
Q

Second messenger ex

A

-ions: Ca+
-water-soluble: cAMP, cGMP, IP3
-lipid soluble: DAG, PIP3

28
Q

Downstream signaling controls

A
  1. Protein phosphorylation
  2. GTP-binding Regulatory Proteins
29
Q

Phosphorylation

A

-mods that control protein-protein interactions and enzymatic activity
-induce conformational change to in/decrease enzyme activity
-promote/disrupt interaction

30
Q

Phosphorylation by Protein Kinase + ATP

A

-activates enzyme

31
Q

phosphatase

A

inactivates enzyme

32
Q

Tyr, Ser, Thr

A

protein phosphorylated on either

33
Q

Promotion of protein interaction via phosphorylation

A

-binding site with phosphorylated residue is recognized by binding partner
-unphosphorylated one is not

34
Q

Disruption of protein interaction via phosphorylation

A

vice versa

35
Q

Recognitionylation

A

Recognition

36
Q

Phospho-Y and phospholipid

A

-large assmebly of proteins from under control of phosphorylation

37
Q

GTP-binding regulatory proteins

A

-exchange of

38
Q

G proteins (GTPases)

A

-bind and hydrolyze GTP to GDP
-off/on switch

39
Q

GDP bound

A

off

40
Q

GTP bound

A

on

41
Q

GTP hydrolysis

A

turns off signal
=GDP

42
Q

Guanine nucleotide exchange factors (GEFs)

A

-catalyze exchange of GDP for GTP
-binds GDP complex to promote GDP release followed by binding of GTP
-ACTIVATES G-protein

43
Q

Cellular Response maximal limit

A

-at lower ligand concentration
-shows amplification without need for ligand engaging all cellular receptors

44
Q

Turn off cellsurface receptors = turn off signaling

A

-reduce level of message or agonist availability in extracellular vicinity of targert cell
-receptor loss/desensitization

45
Q

Reducing availability

A

-common in synaptic signaling
-rapid re-uptake of neurotransmitters by transporters
-serotonin, dopamine, SERT
-breakdown by enzymes

46
Q

Receptor loss/desensitization

A

-reduced receptor availability by internalization and sometimes degradation
-functionally adapted by modifying receptors (de/phosphorylation) to be less active

Biochem (30 decks)

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