Lect. 11 - Signaling Pathways Flashcards
how are signal transduction pathways established?
when a ligand (signaling molecule) binds to a receptor
result of signal transduction pathway
signal being transmitted to the nucleus of a responding cell - responding cell produces gene products that influence the developmental pathway of a cell
Transforming Growth Factor-beta Superfamily (TGF-B1)
disulfide linked dimer; consists of a large proregion and a bioactive region
what forms the dimer in TGF-B1
two bioactive regions after being cleaved from the proregion
what is the purpose of the proregion in TGF-B1 after begin cleaved?
they complex w/ the bioactive dimer to maintain it in a latent form
When does activation occur in TGF-B1?
when the proregions are separated from the bioactive dimer
what part of TGF-B1 functions as the signaling molecule?
bioactive dimer
bone morphogenic proteins
encompasses 15 members w/i TGF-B1 superfamily
what are the modes of action of the bone morphogenic proteins?
inhibit other processes in the embryo, often by being inhibited by other molecules; bind to bioactive dimers and prevent them from binding to receptors
Fibroblast Growth Factor Family number of members
22 members;
FGF family means of regulation
modification of interaction w/ heparan proteoglycans in receptor complex; regulation at membrane of responding cell via transmembrane proteins; regulation by molecules that complex w/ signal transduction machinery
Hedgehog Family
related to the segment polarity molecules in Drosophila; include desert, indian, sonic hedgehog
Wnt Family
includes 18 members in the mouse; related to segment polarity genes in drosophila; often interact w/ components of extracellular matrix; different roles in various vertebrate classes
cell surface receptors w/ intrinsic protein kinase activity
includes receptors for FGF (cytoplasmic domain possesses tyrosine kinase activity) and TGF-beta factors (cytoplasmic domain possesses serine/threonine kinase activity
in the delta-notch pathway, which signal molecule is on the dominant cell?
delta
in delta-notch pathways what is on the neighboring cell?
notch receptor
Delta-Notch pathway actions
proteolytic cleavage of notch in intracellular domain which then complexes w/ Deltex and enters nucleus; complex binds to suppressor of hairless; notch-deltex-suppressor of hairless complex binds to enhanver of split
what is the result signal from the delta notch pathway?
inhibitory signal represses gene expression
lateral inhibition
type of signaling b/w a dominant cell and neighboring cells; the dominant cell is the one that begins to differentiate along a particular path and expresses delta signaling on its membrane.
what happens in lateral inhibition after delta signaling molecule is expressed on the membrane of the dominant cell?
delta binds notch receptors on neighboring cells and represses genes in them (through delta-notch)
receptor tyrosine kinase pathway is used by what kind of signaling molecules?
FGF and TGF-beta
receptor tyrosine kinase pathway components and actions w/ FGF
FGF binds receptor tyrosine kinase; G protein activated (activates RAS, RAF, MAP kinase, and ERK); ERK translocates to nucleus and activates various TFs
receptor tyrosine kinase pathway components and actions w/ TGF-beta
Tgf-beta bind to serine/threonine kinase receptor type II which dimerizes w/ receptor type I (activates R-Smad and Co-Smad); Smad dimer translocates to nucleus and binds to co-factors which can then bind to regulatory factors
Hedgehog pathway
Shh + cholesterol then translocated to cell surface via Dispersed; it inhibited the inhibitory actions of Patched on Smoothened on target cell
