Flashcards in Immune Receptors And Signal Transduction Deck (78)
What do the extracellular domains of receptors recognize?
Soluble ligands or membrane structures of neighboring cells.
How does ligand binding affect a receptor?
It causes a conformational alteration of the receptor.
What is the result of clustering and conformational alterations of a receptor?
It results in changes in the cytosolic portion of the receptor that promotes interactions with other signaling molecules.
What are nuclear receptors?
Intracellular transcription factors that are activated by lipid soluble ligands (estrogen, progesterone, retinoic acid, etc.) that can cross the plasma membrane.
What initiates signal transduction?
The enzymatic phosphorylation of tyrosine, serine or thronine in the cytosolic portion of th ereceptor.
What enzymes are responsible for the phosphorylation of tyrosine, serine or threonine in cytosolic portions of receptors?
What is the function of phosphatases?
They remove the phosphate residues on receptors and modulate signaling.
These phosphatases usually play inhibitory roles in signal transduction.
What other protein modifications facilitate signaling events?
The covalent addition of ubiquitin molecules that either target proteins for degradation or drive signal transduction.
Covalent addition of lipids that promote plasma membrane localization of signaling molecules.
Acetylation and methylation of N-terminal tails of histones, which modulate gene expression, DNA replication and DNA recombination.
What are the three tyrosin kinase families of modular signaling proteins?
These molecules are composed on distinct domains each with a specific binding or catalytic function.
What are unique domains found on modular signaling proteins?
SH2 domains that bind phosphotyrosine-containing polypeptides.
SH3 domains that recognize proline-rich stretches in polypeptides.
PH domains that recognize PIP3 or other phosphatidylinositol derived lipids.
What is the function of tyrosine kinase families?
They are key players in the regulation of immune functions.
What do SH2 domains present, and where does the tyrosine kinase bind to?
SH2 domains present Syk. ZAP-70 tyrosine kinases bind phosphotyrosine motifs in the Ag receptor complex.
What do SH3 domains bind to?
Proline-rich stretches in certain proteins.
What do Pleckstrin homology (PH) domains recognize?
What does Btk tyrosine kinase recognize?
A lipid moiety on the inner leaflet of the plasma membrane termed phosphatidylinositol trisphosphate.
True or false: adaptor proteins lack catalytic activity.
They contain only protein-protein interaction domains.
What do adaptor proteins only contain?
Protein-protein interaction domains.
What are adaptor proteins?
They are molecular hubs that physically link different enzymes and promote the assembly of complexes of signaling molecules.
What domains may an adaptor protein contain?
A few SH2 and SH3 domains.
What amino acid do adaptor proteins contain?
They can contain proline-rich stretches that can bind other proteins that contain the SH3 domains.
They may also contain tyrosine residues that may serve as docking sites for other signaling proteins with SH2 domains.
What is LAT?
An integral membrane protein that functions as an adaptor.
What is GADS?
A cytosolic adaptor protein.
What are the VAV proteins?
Guanine nucleotide exchange factors that activate actin cytoskeletal rearragements and transcriptional alterations.
What do activating receptor contain?
Separate polypeptide chains for recognition and associated signaling poplyeptide chains that contain cytosolic ITAMs.
ITAMs = immunoreceptor tyrosine-based activating motifs.
Where are ITIMs located in inhibitory receptors?
They typically have ITIMS located on the cytosolic protion of the same chain that uses its extracellular domain for ligand recognition.
What is Fc-gamma-RIIB?
An inhibitory receptor found on B cells and myeloid cells.
What does Ag binding and clustering result in?
Activation of an associated Src family kinase.
Once Ag binding and clustering occurs, what type of change occurs?
A conformational change unfolds the cytoplasmic tail of receptor and exposes tyrosine residues of an ITAM motif.
What is the function of Src tyrosine kinase?
It phosphorylates available tyrosines in the ITAMS.