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MCM test 2 > 4- Receptors and Cell signaling > Flashcards

4- Receptors and Cell signaling Flashcards

1
Q

Trophic factors

A

Communicate with cell and tells it to stay alive.

In absence cell will undergo apoptosis

ex. Neurons during early development compete for these factors (Nerve Growth Factor)

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2
Q

Morphogen gradient

A

cell response changes based on concentration

Occurs during development

Signaling Center- cell or group that secretes that message

Responding cells- receives signal and their fate is determined by the concentration of signal
- closer cells have higher number of signals activated…

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3
Q

Desensitization

A

prolonged exposure of signaling decreases cells response to it. (negative feedback with a delay)

Methods

  • Receptor sequestration- ex. in an endosome
  • Receptor down-regulation- shipped to lysosome for degradation
  • Receptor inactivation-
  • Sinaling protein inactivation-
  • Inhibitor protein production-
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4
Q

Mitogen

A

activates cell division

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5
Q

growth factors

A

stimulate cell growth
increase cell mass
-synthesis of biomolecules
-inhibition of factors that degrade biomolecules

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6
Q

Direct cell signaling

A

Cell to cell or cell to matrix

Contact dependent

Gap junctions- channels that allow ions and water to move through cells.
(Gap junctions the only way for direct?)

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7
Q

Endocrine signaling

A

Secreted signals act at distant sites

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8
Q

Paracrine signalling

A

Secreted signal act on nearby cells

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9
Q

Autocrine signalling

A

Secreted signal act on cell that produced them

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10
Q

Synaptic signalling

A

Neurons secrete signal into a synaptic cleft to act on a post synaptic cell.

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11
Q

Steroids

A

Activates intracellular receptor, mostly made from cholesterol

Hydrophobic enough to pass through a cell’s membrane

Binds to nuclear receptor family in cytoplasm, which dimerize upon ligand binding, then translocate to nucleus

Act as transcription factors (activators or repressors)
- can work with coactivators/repressors

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12
Q

Nitric oxide

A

Intracellular receptor, can pass through cell membrane

NO synthase- produces NO from arginine.

NO diffuses fast to neighboring cells but has short half-life so doesn’t effect too far from origin.

Activate guanylyl cyclase–> produces cyclic GMP (2 messenger) –> relaxation of smooth muscle cells

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13
Q

Three general classes of peptides

A

Peptide hormones- diverse, long half-life and distant acting. range in size from 2 to 100s of aa

Neuropeptides- act like neurotransmitters or like hormones

Growth Factors- induce growth, division and differentiation

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14
Q

Neurotransmitters

A

Small hydrophillic molecules.

Released by AP. Signal binds to post synaptic cell and will relate voltage gated ion channels and g protein coupled receptors.

Can perpetuate or inhibit the something in postsynaptic cell

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15
Q

Eicosanoids

Synthesis

A

Act as ligand. Lipid that binds to cell surface receptor

Act locally due to short half life, induce clotting and inflammation.

Phospholipase A: converts phospholipid to arachadonic acid

Cyclooxegenase (COX) converts arachadonic acid to prostaglandins (NSAIDS inhibit COX I and II)

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16
Q

Second Messenger

A

small intracellular molecules or mediators

Generated quickly in large numbers

Diffuse to other parts of the cell.

17
Q

Ion channel coupled receptors

A

Extracellular receptor

Ligand: neurotransmitter

Action: open or close to restrict ion flow and change excitability of cell.

rapid signalling in electrically excitable cells.

18
Q

G protein coupled receptors

Gs, Gi and Gq

A

Extracellular receptor

Ligand: neurotransmitter, peptide hormones, eicosanoids
— special senses: smell, sight, taste

Action: Ligand binding produces confirmational change in receptor. Exchange GDP for GTP (guanine nucleotide exchange factor). BY, and a subunits dissociate and activate targets

Gs: activates adenylyl cyclase
Gi: inhibits adenylyl cyclase
Gq: activates PKC

Deactivation: GTPase activating protein (GAP) hydrolyzes GTP to GDP

Other: 7 pass transmembrane spanning (7TM)

19
Q

Receptor Tyrosine Kinases

A

Extracellular Receptor

Ligand: GH, membrane bound ligands

Action: Ligand binds > they dimerize and cross phosphorlyate each other > phosphorlyate other intracellualr signals or bound by intracellular signaling proteins on phosphotyrosines

Deactivation: Protien tyrosine phosphotases. Remove phosphate group from phosphotyrosine.

Other: contain INTRAcellular tyrosine domain. RTKs exist as monomers in resting.

20
Q

Tyrosine Kinase Associated receptors (TKAs)

A

Extracellular receptor

Ligand: cytokines, interlukins, integrins

Action: Ligand binding causes receptor dimerization
Soluble RTKS associated with the plasma membrane are activated. DOESN’t Phosphorylate itself. Tyrosine Kinase protein does.

Monomers on rest.

21
Q

Cytokine Receptor

A

Extracellular Receptor

Ligand: cytokines and some hormones

Action: Tyrosine Kinase ASSOCIATED receptor. like TKA but uses JAK/STAT

Deactivation: Protien tyrosine phosphotases. Remove phosphate group from phosphotyrosine.

22
Q

Receptor Guanylyl cyclases

A

Extracellular receptors

Ligand:

Action: Catalyzes the formation of cGMP

23
Q

Receptor Serine/Threonine Kinases

A

Extracellular

Ligand: TGF-beta

Action: 
Form heterodimers
One chain phosphorylates the other
Activated receptor phosphorylates Serine and Threonine residues
Activated Smad pathway
24
Q

Notch

A

Extracellular

Ligand: delta

Action: Delta binds, gamma secretase(proteolytic) cleaves tail of Notch into cytosol. Tail to nucleus and acts as transcription factor.

Other: direct cell-to-cell signaling.

25
Q

Frizzled

A

Extracellular

Ligand: Wnt

Cytosolic protein b-catenin is normally phosphorylated, ubiquitinylated and degraded

Action: Ligand binding to the receptor recruits the complex responsible for b-catenin phosphorylation.

b catenin no longer getting phosphorylated. Translocates to nucleus, induces transcription with TF.

26
Q

Patched

A

Extracellular

Ligand: Hedgehog

Action:
Ligand binding activates Smoothened (transmembrane protein)
Smoothened inhibits phosphorylation of Ci
Ci translocates to the nucleus to induce transcription

27
Q

Death Receptors

A

Extracellular

Ligand: Cytokines, growth factors or Pathogen Associated Molecular Patterns (PAMPs)

Action: One ligand binds to all three subunits, then it induce clustering of cytosolic death domains, apoptosis follows.
Adaptor proteins with Death Domains are recruited and activated

Other: Activates Extrinsic apoptosis or inflammation. Heterotrimeric at resting

28
Q

Integrins

A

Extracellular receptor

Ligand: GF and trophic factors

Action: Clustering of integrins induces autophosphorylation of FAKs (Focal Adhesion kinases)
Phosphorylation sites serve as binding sites for signaling proteins
- Induce proliferation, gene expression and survival

Other: Focal Adhesion, hemidesmosomes (at cell-matrix junctions)

29
Q

cAMP

Synthesis and action

A

Second Messenger

synthesis: Formed from AMP by adenylyl cyclase
Degraded to AMP by cAMP phosphodiesterase

Action: Activates Protien Kinase A which is a Tetramer, (two regulatory and two catalytic subunits) cAMP binds reg unit and catalytic subunits dissociate and phosphorylate targets.

30
Q

cGMP

Synthesis and action

A

second messenger

Synthesis: Formed from GTP by guanylyl cyclase
Degraded to GMP by phosphodiesterase

Action: Activates protein kinases, ion channels and phosphodiesterases

31
Q

Phosphatidylinositol 4,5 bisphosphate (PIP2)

A

Component of inner leaflet of plasma membrane

Inside phospholipid

32
Q

Phospholipase C

A

Phospholipase C hydrolyzes PIP2 to :

IP3- activates ligand gated calcium channels in ER to increase cytosolic Ca and activate Ca sensitive proteins.

DAG- activates protein kinase 3

33
Q

PI3 kinase

A

Phosphoryates PIP2 to PIP3

Activates Akt– kinase that influences cell survival and protein synthesis

34
Q

MAP (mitogen activated protein) kinase

A

Mitogen or growth factor activated protein kinases.

Regulates cell growth and differentiation. RAS is active when bound to GTP (formed by GEF) and inactive when bound to GDP (formed by GAP)

Ras phos RAF. RAF phos MEK. MEK phos ERK. ERK will phos down stream targets.

35
Q

JAK/STAT

A

goes with Cytokine receptors

The receptor associated tyrosine kinase is JAK, this will get phos when cytokine binds then it will phos STAT, two STAT will dimerize and will then go be transcription facto

36
Q

TGF beta/SMAD

A

Protein-serine/threonine kinases activated when bound to TGF-b

Phosphorylate Smads
Smads translocate to nucleus and act as transcription factors

37
Q

NFkB

A

Receptor responds to TNF, cytokines, GF, and PAMP

NFkB usually bound to IKB inhibitor protein in cytosol

Activation of the receptor activates IkB kinase
IkB is phosphorylated
IkB is ubiquitinylated and degraded by proteases
NF-kB translocates to the nucleus and acts as a transcription factor

38
Q

Rho

A

Regulates cytoskeletal changes. Activated by integrin and GF receptors

Promotes actin polymerization
Promotes phosphorylation of myosin

MCM test 2 (15 decks)

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