Lecture 3 -Quiz 1 Flashcards
(48 cards)
What does the binding of signaling molecule to receptors induce?
Change in protein function or change in gene expression
What types of molecules are used as signals in extracellular signaling?
Amino acids, peptides, soluble molecules like insulin, tethered proteins, gases
At what distance can extracellular signaling work?
Locally and over great distance
What is endocrine extracellular signaling?
A distant target cell - hormones, insulin
What is paracrine extracellular signaling?
Adjacent not touching cells - neurotransmitters
What is autocrine extracellular signaling?
Sites on the same cell secreting - growth factors
What is juxtacrine extracellular signaling?
Plasma membrane attached between touching cells like notch
How do ligands bind to receptors?
Molecular complementary
How do most ligands form receptor dimers?
They bind a receptor but recruit another by using same binding surface but a different area
What does the conformation of GTP switch proteins look like when bound to GTP?
GTP adding another phosphate creates a bridge to the switch arms that fold in slightly
What are second messengers and list a few
Small molecules that act to convey signal and amplify it - Ca++, cAMP, cGMP, DAG, IP3
What is Kd and what is the formula?
It is the concentration of ligand at which half of the receptors for that ligand are occupied (affinity measure) – Kd = [R][L]/[RL]
What is important to determine the response of a ligand?
Receptor number and Kd – finding the balance between the affinity and number – want to ideally have both with high numbers
What is the general setup of a binding assay?
Radiolabled lignad response in two cell lines one with specific receptor and one without and count - subtract out background from nonspecific binding of no receptor to determine specific binding of total receptor – can then find half of the bound value to determine Kd
How could you find Kd for a low affinity ligand?
Perform a binding assay with competition by using a low affinity and high affinity ligand, the point at which the low affinity outcompetes the high affinity = Kd
What pathways can Receptor tyrosine kinase and JAK kinase activate?
STAT, GRB2, Phospholipase C, PI-3 kinase
What is the general structure and activation of receptor tyrosine kinases (RTKs) - What is an example
Need ligands to bind to two separate monomer receptors to dimerize and create activation – intracellular kinase domain becomes activated so that they can phosphorylate eachother and continue the phosphorylation - HER OR EGFR family
How does the binding of HER1 and HER4 work and what is a receptor example for HER1?
It works just like a typical RTK requiring two ligands to bind to two monomer receptors to dimerize - EGFR
How does the binding of HER2 work and what is it problematic for?
HER2 is constitutively activated and always on, it can bind to any of the other receptors but not to ligand - bad in breast cancer
What does HER3 need to do to become activated?
Only gets signal when bound to HER2 - does not have an activated kinase region
What is the general structure and activation of cytokine receptors?
Only one ligand is needed to bring 2 receptors together to produce dimerization and activation intracellularly of the JAK kinase - humans have 4 JAK kinases
What can bind to phosphotyrosine residues in the kinases to amplify signal?
SH2 domains or PTB domains
How does STAT proteins become activated?
After SH2 binding, STAT is brought closer to active JAK associated with the receptor and JAK phosphorylates STAT causing STAT to dissociate from receptor and spontaneously dimerize – dimer moves to nucleus and binds promoter sequences to activate transcription
What is the primary way to terminate cell signaling?
Endocytosis to be degraded (if high levels of ligand are present)
