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eBMS2021 > TOPIC B: Cell signalling > Flashcards

TOPIC B: Cell signalling Flashcards

1
Q

What does amplification mean

A

The number of affected molecules increasing geometrically due to a signalling cascade

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2
Q

What are the 4 types of signalling + basic description

A

Contact dependent: cells in contact

Paracrine: released to neighbouring cells

Synaptic: Neurotransmitters at a synapse

Endocrine: hormones in bloodstream

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3
Q

What are the 3 main classes of hormones + basic description

A

polypeptide/protein: Stored in secretory vesicles

amide hormones: developed from tyrosine like epinephrine and norepinephrine

steroid hormones: steroids similar in structure (cholesterol)

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4
Q

What are the two main types of molecular switches + basic description

A

phosphorylation: kinase and phosphatase deactivate or activate

binding of GTP: exchange of GDP for GTP activates.

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5
Q

What are the 2 broad types of receptors

A

Cell surface receptors

Intracellular receptors

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6
Q

What are the 3 types of cell surface receptors

A

Ion channel coupled receptor

G protein coupled receptor

Enzyme coupled receptor

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7
Q

What is the 1 type of intracellular receptor

A

Nucelar receptor

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8
Q

What is an enzyme linked receptor

A

cell surface receptors linked intracellular enzymatic activity. Trigger a cascade.

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9
Q

What are the 2 types of enzyme linked receptors studied in this course

A

receptor tyrosine kinases

tyrosine kinase associated receptors

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10
Q

Describe activation of a receptor tyrosine kinase

A

when activated phosphorylate intracellular Tyr residues.

RTKs dimerise and then trans auto phosphorylation occurs.

Phosphorylation of tyrosine kinase domain acts as docking sites.

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11
Q

What is a domain of a docking, adaptor or scaffold protein

A

Specific parts of protein which recognise certain regions on other proteins.

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12
Q

Define a docking protein

A

Proteins embedded in the cell membrane, allows other proteins to dock to them

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13
Q

Define an adaptor/scaffold protein

A

Protein that links/bridges one protein to another if they cannot bind to the receptor themselves. Allows further activation

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14
Q

Explain the complex formed at the insulin receptor

A

insulin receptor is a receptor tyrosine kinase.

IRS1 binds when it is phosphorylated which allows other proteins to attach and become activated.

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15
Q

Describe the MAPK pathway of a receptor tyrosine kinase

A

Insulin RTK activated causing binding of IRS1.

Grb2 binds to IRS1 allowing Ras-GEF (Sos) to bind and become activated.

Sos activates Ras protein by GDP/GTP exchange.

Ras activates Raf. Raf activates Mek which activates Erk by phosphorylation.

Erk phosphorylates proteins causing cell proliferation/growth/differentiation

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16
Q

Describe the PI3K/Akt pathway of a receptor tyrosine kinase

A

Insulin RTK activated causing binding of IRS1.

PI3K binds activating it, causing it to phosphorylate docked inositol phospholipids.

This allows protein kinase 1 to dock and with protein kinase 2 phosphorylate and active Akt.

Akt causes multiple cell responses explained in different question

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17
Q

What are the cell responses due to Akt activation

A

Phosphorylates Bad causing dissociation and activation of Bcl2 causing cell survival.

Protein synthesis, glycogenesis, gluconeogenesis, lipogenesis in liver

GLUT4 translocation and glycogenesis in muscle

GLUT4 translocation, lipogenesis in adipose

18
Q

What is a tyrosine kinase associated receptor

A

Enzyme linked receptor that couple to proteins that have Tyr kinase activity.

19
Q

Outline the activation of cytokine tyrosine kinase associated receptors

A

Cytokine binds causing dimerisation of receptors

JAK protein already attached to monomers is then activated causing them to phosphorylate each other and then the receptor.

This provides binding sight for STAT proteins which then form complex that travels into the nucleus and activates transcription.

20
Q

Describe a ligand gated ion channel

A

A cell surface receptor also called an ion channel coupled receptor.

open or close in response to a ligand

21
Q

Outline the physical characteristic of a GPCR

A

Cell surface receptor

7 transmembrane segments

extracellular N, intracellular C

22
Q

Define a G protein

A

guanine nucleotide binding proteins act as molecular switches by binding GTP to other proteins in the cell

23
Q

What enzymes activate and deactivate a G protein

A

Guanine nucleotide exchange factor (GEF): swaps GDP for GTP, activates

GTPase activating protein (GAP): hydrolyses GTP to GDP, deactivates

24
Q

Describe the trimeric complex of a G protein

A

alpha, beta and gamma units.

alpha unit works on its own as a GTPase

Beta and gamma work together

25
Q

Explain the activation of a G protein from a GPCR

A

GPCR activated by signalling molecule

GPCR interacts with G protein

G protein ejectes GDP for GTP, causing activation and releases beta gamma unit.

unit activates other proteins delivering message throughout cell

turned off when GTP is hydrolysed to GDP.

26
Q

Define an effector enzyme and a second messenger

A

Effector enzyme:
More enzymes activated by a G protein or earlier protein in pathway

Second messengers:
affect later parts of pathway and are activated by effector enzymes

27
Q

Explain the activation of the inositol phoshpolipid GPCR pathway

A

GPCR activated causing activation of G protein

beta gamma unit activates phospholipase C (effector enzyme in membrane)

phospholipase C cleaves PIP2 into DAG and IP3 (second messengers)

IP3 targets Ca channels of E.R causing Ca release

Ca and DAG activate protein kinase C which activates cell response

28
Q

Explain the activation of the cAMP GPCR pathway.

A

GPCR and G protein activated

unit activates adenyl cyclase to convert ATP to cAMP (second messenger)

cAMP activates protein kinase A by binding to catalytic subunits, goes onto activate cell response

29
Q

Briefly explain how adrenaline and GPCR causes glycogenolysis

A

adrenaline activates GPCR and G protein

cAMP pathway activates glycogen phosphorylase

30
Q

Briefly explain how adrenaline and GPCR causes increased gene transcription.

A

adrenaline activates GPCR and G protein

cAMP pathway activates molecules for gene transcription to move into the nucleus

31
Q

Outline the stimulation pathway for cortisol production

A

ACTH release from anterior pituitary in response to CRH from hypothalamus.

Stimulates cortisol production pathway in adrenal cortex

32
Q

Describe cushins syndrome

A

chronic exposure to cortisol causes decreased growth in children, weight gain, hypertension, diabetes, osteoporosis.

Treatment includes adrenalectomy or steroid replacement

33
Q

What are the three main types of steroid hormones and the examples of them produced in the cholesterol pathway

A

Mineralocorticoids

Glucocorticoids

Androgens

34
Q

What are the three main types of steroid hormones and the examples of them produced in the cholesterol pathway

A

Mineralocorticoids: Aldosterone

Glucocorticoids: Cortisol

Androgens: Testosterone

35
Q

What is a nuclear receptor

A

An intracellular receptor activated by lipophilic ligands as they can diffuse across cell membrane.

36
Q

Describe the mechanism of nuclear receptor action

A

Ligand activates nuclear receptor

induces homo or hetero dimerisation as well as binding of dimer to DNA

Coactivator recruitment increases target gene transcription by binding to nuclear receptor

Altered levels of the hormone regulated gene product produce cellular response

37
Q

What are the 2 types of estrogen receptors

A

alpha and beta

38
Q

What is ERalpha important for

A

Female reproduction

mammary gland function

bone, CVS, brain

39
Q

What is ERbeta important for

A

ovary, bone, brain, male prostate

40
Q

Outline a selective estrogen receptor moedulator (SERM)

A

Mimic estrogen receptor ligands to help treat disease

ER agonist is BPA, stimulates over transcription causing birth defects

ER antagonist if tamoxifen, which treats breast cancer, by binding to ER, preventing ER mediated gene transcription

41
Q

Briefly describe chronic myeloid leukaemia

A

caused by oncogenic tyrosine kinase called BCR-ABL

overproduction and overflow of immature WBC and uncontrolled cell growth and proliferation

Gleevec binds BCR-ABL preventing ATP from binding

42
Q

Briefly explain monoclonal antibodies

A

Can target cell surface receptors to stop disease by binding to receptor instead of ligand.

Herceptin can bind to HER2 inhibiting activation of signalling pathways. Can be used to treat HER2 positive breast cancer.

eBMS2021 (8 decks)

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