Exam 3 Theisen review PART 1 Flashcards
4 types of cell signaling (based on distance)
- Endocrine signaling 2. Paracrine signaling 3. Autocrine signaling 4. Direct cell signaling (Juxtacrine signaling)
Endocrine signaling:
Long distance signaling Signal –> Bloodstream –> distant target signal -freely diffuse signal -long lasting/ long half-life in minutes -takes time to go through the circulatory system to find a target cell ** Hormones
Paracrine signaling:
acts locally -affects cells nearby (not as freely diffusible) -short lived signal -** neurotransmitters
Autocrinesignaling
-cells respond to their own signals, or release to cells of the same type. -cells release signal that feeds back and binds to a receptor on its own surface. -** growth factors in cancer. Paracrine signal —> autocrine signal —> cells to mature.
Direct cell signal (juxtacrine signaling) :
-Cell to cell contact. ** immune cells —- APC to T-cells
Each cell interprets the combination of all these types of signaling to determine what to do:
-survive -divide -differentiate -die
Cell surface receptors:
most signaling molecules are hydrophilic and require cell-surface receptors
Intracellular receptors
Small hydrophobic signaling molecules can diffuse across the cytoplasmic membrane and bind to intracellular receptors.
What are the three main types of cell signaling receptors in the plasma membrane?
-Gated ion channels common in nervous tissue. - GPCRs use t-pass transmembrane proteins. -Enzyme-coupled receptors class included receptor tyrosine kinases (RTKs)
List the steps in signaling by trimeric G-proteins
-inactive -activation or receptor by ligand binding. -activated receptor binds to G-protein (acts as GEF). -G-alpha releases GDP and binds GTP, and dissociates from G-beta-gamma. -G-alpha binds and activates adenylyl cyclase. -G-alpha hydrolyses GTP to GDP, dissociates from adenylyl cylcase and binds G - Beta-Gamma (inactive)
Signal amplification in the cAMP pathway
-1 signal ligand bind with receptor protein -each activated receptor protein may activate many molecules of Gs protein, which liberates and alpha subunit that can activate an adenylyl cyclase molecule for a prolonged period. -each adenylyl cyclase generates many cAMP molecules. -cAMP molecules activate A-kinase (PKA) -each PKA can phosphorylate and activate many copies of enzyme X. -each copy of enzyme X produces many molecules of substrate/product. **** leads to amplification.
How does cAMP cause a biological response?
it interacts with its target proteins,. -cAMP activates cAMP-dependent protein kinase (PKA)-4 subunits. -Inactive PKA:2 catalytic subunits & 2 regulatory subunits binding to 2 cAMP molecules to regulator subunits of tetramer results in release of active Catalytic subunits.
Receptor tyrosine kinase activity
-RTK bins to SH2 of Grb2. -Grb2 also has SH3 domain. -SH3 of Grb2 binds to prolines of SOS (son of sevenless), which then binds to Ras (small monomeric G protein -Small GTPase). -Ras discovered in human oncogene, plays crucial role in cell division and frequent mutation in cancer. - Ras Binds Raf and then thing get insane.
What is downstream of Ras?
Ras recruits Raf to plasma membrane and helps activate it. Raf ( MAP kinase kinase Kinase) helps activate MAP Kinase Kinase (Mek), which helps activate Map Kinase (Erk). -Erk in turn phosphorylates a variety of downstream proteins. including other protein kinases and transcription regulators.
What can occur between G-protein-coupled receptor pathways and protein tyrosine kinase receptor pathways?
Cross-talk
