4- Receptors and Cell signaling

Question 1

Trophic factors

Answer 1

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)

Question 2

Morphogen gradient

Answer 2

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…

Question 3

Desensitization

Answer 3

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-

Question 4

Mitogen

Answer 4

activates cell division

Question 5

growth factors

Answer 5

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

Question 6

Direct cell signaling

Answer 6

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?)

Question 7

Endocrine signaling

Answer 7

Secreted signals act at distant sites

Question 8

Paracrine signalling

Answer 8

Secreted signal act on nearby cells

Question 9

Autocrine signalling

Answer 9

Secreted signal act on cell that produced them

Question 10

Synaptic signalling

Answer 10

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

Question 11

Steroids

Answer 11

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

Question 12

Nitric oxide

Answer 12

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

Question 13

Three general classes of peptides

Answer 13

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

Question 14

Neurotransmitters

Answer 14

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

Question 15

Eicosanoids

Synthesis

Answer 15

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)

Question 16

Second Messenger

Answer 16

small intracellular molecules or mediators

Generated quickly in large numbers

Diffuse to other parts of the cell.

Question 17

Ion channel coupled receptors

Answer 17

Extracellular receptor

Ligand: neurotransmitter

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

rapid signalling in electrically excitable cells.

Question 18

G protein coupled receptors

Gs, Gi and Gq

Answer 18

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)

Question 19

Receptor Tyrosine Kinases

Answer 19

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.

Question 20

Tyrosine Kinase Associated receptors (TKAs)

Answer 20

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.

Question 21

Cytokine Receptor

Answer 21

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.

Question 22

Receptor Guanylyl cyclases

Answer 22

Extracellular receptors

Ligand:

Action: Catalyzes the formation of cGMP

Question 23

Receptor Serine/Threonine Kinases

Answer 23

Extracellular

Ligand: TGF-beta

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

Question 24

Notch

Answer 24

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.

Question 25

Frizzled

Answer 25

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.

Question 26

Patched

Answer 26

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

Question 27

Death Receptors

Answer 27

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

Question 28

Integrins

Answer 28

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)

Question 29

cAMP | Synthesis and action

Answer 29

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.

Question 30

cGMP | Synthesis and action

Answer 30

second messenger Synthesis: Formed from GTP by guanylyl cyclase Degraded to GMP by phosphodiesterase Action: Activates protein kinases, ion channels and phosphodiesterases

Question 31

Phosphatidylinositol 4,5 bisphosphate (PIP2)

Answer 31

Component of inner leaflet of plasma membrane Inside phospholipid

Question 32

Phospholipase C

Answer 32

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

Question 33

PI3 kinase

Answer 33

Phosphoryates PIP2 to PIP3 Activates Akt-- kinase that influences cell survival and protein synthesis

Question 34

MAP (mitogen activated protein) kinase

Answer 34

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.

Question 35

JAK/STAT

Answer 35

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

Question 36

TGF beta/SMAD

Answer 36

Protein-serine/threonine kinases activated when bound to TGF-b Phosphorylate Smads Smads translocate to nucleus and act as transcription factors

Question 37

NFkB

Answer 37

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

Question 38

Rho

Answer 38

Regulates cytoskeletal changes. Activated by integrin and GF receptors Promotes actin polymerization Promotes phosphorylation of myosin