intracellular signallin Flashcards

1
Q

give 4 examples of cellular responses

A
  • change metabolic activity e.g. glucagon
  • secrete and release e.g. mast cell and histamine
  • changes in gene expression e.g. epidermal growth factor (EGF) activate genes
  • sensory perception e.g. light activation of rhodopsin
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2
Q

what acts as extracellular signals? 5

A
  1. amino acids (adrenaline, dopamine, glutamate…)
  2. steroids
  3. prostaglandins (eicosanoids) - derived from arachidonic acid
  4. proteins and peptides
  5. gases (NO, CO)
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3
Q

4 examples of steroids

A

ortisol, aldosterone, testosterone, oestradoil

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4
Q

4 examples of proteins and peptides used in extracellular signalling

A

insulin
glucagon
growth factor
EGF

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5
Q

5 ways for cells to signal to EACH OTHER

A
  • endocrine
  • autocrine: acts on same cell
  • paracrine: close by
  • contact dependent (Signal is integral part of one cell and interacts directly with another cell)
  • neuronal
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6
Q

what kind of substance do cell surface receptors bind to

A
  • hydrophilic hormone e.g. adrenaline

- trigger response inside cell

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7
Q

what substances do intracellular receptors bind to

A
  • hydrophilic hormones e.g. steroid hormones

- bind to receptor inside cell

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8
Q

types of signalling when signal is bound to receptor and examples

A
  1. depolarisation of membrane due to ion flow e.g. ACh
  2. directly activate transcription factor e.g. steroid
  3. generate secondary messenger e.g. glucagon - cAMP
  4. direct activation of enzymatic kinase cascade e.g. EGF - MAP kinase pathway
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9
Q

what substances are involved with signalling by membrane depolarisation

A

ion channels e..g ACh binding to nicotinic acetylcholine receptor
Na, K, Ca ions

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10
Q

describe activaton of transcription factors

A
  • steroid hormones contain hormone binding domain, DNA domain and domain to interact with other trans factors
  • binding of steroid = conformational change = DNA binding and activation of target genes
  • hormone response elements in sequence of target genes
  • ligand-dependent transcription factors
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11
Q

Give 5 examples of secondary messengers

A
cAMP
IP3/DAG
Ca2+
nitric oxide
cyclic GMP
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12
Q

examples of secondary messengers generated by enzymes - GPCR (G protein coupled receptor)

A

– Activate adenylyl cyclase (adenylate cyclase)
• adenosine 3’:5’- cyclic monophosphate (cAMP)

-Activation of phospholipase C
• inositol 1,4,5-trisphosphate (IP3)
• 1,2-diacylglycerol (DAG)

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13
Q

what’s an example of a GPCR

A

B-adrenargic receptor e.g. adrenaline

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14
Q

what happens when a G-protein is activated

A
  • hetrotrimeric complex
  • dissociates when GTP binds.
  • Free Ga subunit activate effector enzymes which produces 2nd messenger
  • re-associates when GTP hydrolysed to GDP by GTPase
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15
Q

what does G protein dissociate into

A

GTP - alpha-bound subunit

By (beta-gamma) subunits

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16
Q

describe the structure of cAMP dependent PKA

A

-tetrameric enzyme

2 regulatory, 2 catalytic subunits R2C3

17
Q

how does cAMP activate PKA

A
  • cAMP binds to regulatory subunit on PKA = dissociates

- catalytic monomers are active enzymes

18
Q

ATP –> cAMP –> AMP enzymes

A

adenylyl cyclase

phosphodiesterase

19
Q

how does cAMP and PKA action affect gene expression

A
  • PKA phosphorylates CREB (cAMP response elementat binding protein)
  • CREB binds to sequences. in target genes - stimulate transcription
20
Q

what does the Gq (Gaq) subunit in some GPCR do

A
  • dissociated Gaq subunit activates phospholipase C
  • cleaves inositol phospholipids in membrane (IP3, DAG)
  • IP3 activates Ca channel in ER
  • DAG and Ca activates protein kinase C
21
Q

how does the binding of EGF activate

A
  • autophosphorylates tyrosine residues in intracellular RTK
  • proteins contain phosphotyrosine binding sites: SH2 and PTB
  • adaptor roteins Grb2 and Sos bind to receptor
  • activates exchange GDP-Ras–> GTP-Ras
22
Q

what is Ras and describe the Ras-MAPkinase pathway

A
  • monomeric G protein
  • triggers kinase cascade
  • MAPKKK activates MAPKK actives MAPK –> activates transcription factor
  • no secondary messenger
23
Q

what does MAPK stand for

A

mitogen activated protein kinase

24
Q

what are the 2 types of overlap in intracellular signalling (i.e. one hormone for different receptors)

A
  • convergence: different signals trigger diff pathways but same effect
  • Cross talk: diff signals trigger diff pathways that block each other
25
Q

give an example of cross talk overlap

A
  • EGF signalling via PTK and Ras-MAPK

- adrenaline inhibits one of the steps via action of PKA

26
Q

what does IP3 and DAG stand for

A

Inositol 1, 4, 5 trisphosphate

Diacylglycerol

27
Q

what are the phosphotyrosine binding proteins in adaptor proteins in the activation of kinase cascade

A

SH2 (sos - homology 2)

PTB (phosphotyrosine binding)

28
Q

what adaptor proteins bind to the receptor in activation of kinase cascade - EGF

A

Grb2 and Sos