Cell to Cell Signaling
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3 major types of interactions between adjacent cells? Where are they found in?
Connexins: Connect & Share Cytoplasm
Found inbetween neurons, smooth muscle cells, cardiac tissue, bone celle.
Give example nd definition of contact dependent cells.
Bind to surface of cell membranes
Name Long Distance Chemical Coupling
What do they do?
- Neurocrines: Chem made by neurons
- Neurohormones: chem made by neurons made in hypothalamus
Neuromodulators: chem made by neurons to alter 2nd messenger response.
What do cytokines do?
- cell development,
- Cell differentiation,
- & Immune response
Distance: both short and long distance
What are three components of cell signaling?
- Extracellular First messengers
- Intracellular Second Messengers
Types of competition:
ex of each
- Agonist: attaches and mimics first messenger
- Ex: Ephederine
- Antagonist: get in way of receptors, deactivating them.
- Ex: Beta blockers to lower BP
What happens when there is too much first messengers?
- Down Regulation
Receptors are still there but not the active site.
What happens when there is too little first messengers?
An increase of sensitivity of binding sites + more FM
What are the Short distance local signal cells?
Paracrines: Chem made by neurons, signal neighbor cells
Autocrines: Chem made by themselves for itself.
mediator cells between FM and SM found in cell membrane or cytosol
What do secondary messengers do?
Stimulate a cell response
Give some examples of what some of the first messengers are:
- Local Chemical Mediators
- a. paracrines
- b. autocrines
- c. Cytokines
Water-Soluble or Lipophobic act on
receptors in cell membrane.
Lipophobic WILL NOT dissolve in lipid bilayer
Lipid Soluble or Lipophillic act on
receptors in cytoplasm or nucleoplasm of cell
Amplifier enzyme activates a secondary messenger
Process by which stimulus is transformed into cell response.
What is an example of
Ligand-Gated Ion Channels
Nicotinic attaches in place of ACH (adrenaline)
Ligand-Gated Ion Channels
Open/close by a receptor that attaches and acts as ion channel directly
Proteins can work as:
Receptor-enzymes are all...
Protein Kinases except for one guanylyl cyclase activity
Recptor Tyrosine Kinases
- Binding of messenger to receptor on cytoplasmic side of PM.
- Tyrokinase = Activated = Insulin Receptor Attaches
- Bind and activate other proteins
- Glut 4 activated to insert into membrane Guanylyl Cyclase funcs as receptor & Cyclic-GMP as second messenger
Receptors that stimulate G proteins:
- Alpha --> GDP & GTP
- Betta & Gamma --> Help anchor Alpha
- Binding of FM Occurs On receptor
- Activated receptor = higher affinity for Alpha
- Alpha disassociates from betta/gamma
- Allows alpha to bind to other PM proteins
- (ion channel or enzyme thus called effector proteins)
- G-protein cples recept to effector proteins
- Activated effector GTP-ase to cleave GTP into GDP + P1
This renders alpha subunit inactive allowing to recombine w/ its betta and gamma sub units.
What makes up a G-Protein?
- Bound to inactive receptors is a protein complex located on cytoplasmic side of Plasma membrane.
- (alpha beta gamma)
Receptors that generate cyclic-AMP as SM (pathway
Signal pathways must be terminated via any one of these:
- Remove the First Messenger(Brk dwn FM enz)
- Inactivate Receptors(PO4/Endo/ClathPIT)
- Removal of second messenger
- (rmvl of F.M or break down 2nd Messenger)
What had First messengers but no receptors?
THESE DIFFER FROM OTHER CHEMICAL MESSENGERS
Examples of drugs aimed at transduction
Pathway initiated by Lipid-Soluble Messengers
- M binds 2 inactive receptors in nucleus
- Gene Transcription
- Diffuses out capillaries/across P.M Binds 2 rec in nucleus
- Transcription factors
- mRNA move out of nucleus synthesizes on ribosomes
- Cells ultimate response
Pathway initiated by Water-soluable messengers.
- Bind 2 extracellular portion on PM
- Secondary messenger in cytoplasm activated
- Diffuses through PM
- Protein Kinase
- Cell Response
What are signaling for water soluble molecules?
Receptors/channels: ex Nicotinic receptor
Receptor/Enz: ex: Guanacyc. Tyr. Kinase GMP
Which pathways fall under PLASMA-MEMBRANE RECEPTORS pathway category?
- a. Receptors that themselves function as ion channels.
- b. Receptors that themselves function as enzymes.
- c. Receptors that are bound to and activate cytoplasmic JAK kinases.
- d. Receptors that activate G proteins, which in turn act upon
- effector proteins—either ion channels or enzymes—in the plasma membrane.
Which pathway is associated with intracellular receptors?
- lipid-soluble messengers)
- Function in the nucleus as transcription
- factors to alter the rate of transcription of particular genes.
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