Final: Ch 16 Notch/Delta, SREBP, Integration Flashcards
MMP
matrix metalloprotease
metal containing enzymes that cleave the extracellular segments of target proteins near the outer membrane
in the Notch/Delta pathway, ___ cleavage of the extracellular part of the Notch receptor is followed by its cleavage within the plasma membrane by a different protease, releasing the _____ domain that functions as a ___
MMP, cytosolic, TF
upon binding Delta, the _______ receptor is cleaved and releases a component ___
Notch, TF
are the receptor Notch and its ligand Delta single spanning transmembrane proteins found on the cell surface?
yes
when Delta on one cell binds Notch on another cell what happens
activated Notch undergoes two cleavage events
these result in the Notch cytosolic domain being released and functioning as a TF
2 cleavage events Notch undergoes
ADAM cleaves the extracellular segment of Notch
Secretase cleaves the cytosolic segment of Notch, which translocates to the nucleus
Delta and Notch are initially equivalent, but _____ Delta on the target cell and ________ expression of Delta on the source cell
decreases, increases
what is disintegrin
a protein domain that binds integrins and disrupts cell-matrix interactions
lateral inhibition
a process where adjacent cells achieve different fates
ex. Notch forms a complex with SuH to transcribe genes whose effect is on cell fate
Notch increases, and Delta decreases
many signaling molecules are synthesized as transmembrane proteins whose signal domain extends into the _________ region… ex.
extracellular
ex. Delta
many growth factors and other proteins are synthesized as transmembrane ______ whose cleavage results in….
precursors
cleavage releases soluble active signaling molecule into the extracellular space
what class of protein are the ADAM family and what can heightened ADAM activity result in?
MMPs
increased activity is seen in cancers (high levels of EGF, destroys ECM to facilitate metastasis)
inappropriate cleavage of amyloid precursor protein can lead to _________ disease
Alzheimer’s disease
amyloid plaques accumulate from cleavage ofamyloid precursor protein (APP)
proteolysis of SREBP releases a __________ _______ that acts to maintain __________ and ________ levels
transcription factor, phospholipid, cholesterol levels
LDL
low density lipoprotein
rich in cholesterol and transports it through the circulatory system
both the cholesterol biosynthetic pathways and cellular levels of LDL receptors are ____-______ when cellular levels are adequate
down-regulated
SRE-binding protein (SREBP)
cholesterol-dependent transcription factors
interact with sterol regulatory elements in the promoters to modulate expression of genes
when cells have ______ cholesterol, SREBP is found in the ___ membrane complexed with SCAP, insig-1, and other proteins
adequate, ER membrane
when cholesterol levels drop sufficiently what happens
SCAP releases cholesterol and the SCAP-SREBP complex moves from the ER to Golgi via COPII vesicles
SREBP is cleaved twice and nuclear SREBP moves to the nucleus and activates transcription of genes with sterol regulatory elements in promoters
result of nuclear SREBP
expression of genes that import cholesterol into the cell (LDL receptor)
expression of genes that synthesize cholesterol like HMG-CoA reductase
does SCAP recycle back to the ER?
yes
what do statins do
reduce plasma LDL
bind HMG-CoA reductase to inhibit it
increase # of LDL import receptors in liver
maintenance of blood glucose concentration depends on which two hormones
insulin (beta cells)
glucagon (alpha cells)
insulin _______ the level of blood glucose
reduces
glucagon ______ the level of blood glucose
increases
what happens to blood glucose after a meal
raises above normal level, and pancreatic beta cells release insulin (binds receptors)
insulin binding insulin receptor tyrosine kinase activates protein kinase B
what does protein kinase B do after it’s activated by insulin tyrosine kinase receptors
phosphorylates a target protein that triggers the rapid fusion of vesicles containing the glucose transporter GLUT4 with the membrane
this lowers blood sugar
insulin stimulation of muscles cells does what…
enhances conversion of glucose into glycogen
PKB activates glycogen synthease
insulin stimulation effect in liver cells…
inhibit glucose synthesis
when blood glucose drops normally what happens
GLUT4 receptors are internalized and glucose import lowers
if blood glucose drops too much what happens
glucagon is secreted in liver cells, causing a rise is cAMP –> PKA
PKA inhibits glycogen synthesis and promotes glycogenolysis to yield glucose –> released into blood
diabetes mellitus
deficiency in insulin released in response to increased blood sugar (type I) - autoimmune destruction of insulin producing beta cells
impaired ability of muscle/fat to respond to insulin (type II)
multiple signal transduction pathways interact to regulate ________ differentiation through _____ the master transcriptional regulator
adipocyte, PPAR-gamma
what are the major cells for storing fats
white adipocytes
are adipocytes also endocrine cells that secrete signaling proteins?
yes
PPAR-gamma
a transcription factor member of the nuclear receptor superfamily
master transcriptional regulator of adipocyte differentiation
a knockdown of the gene for PPAR-gamma in preadipocytes does what
prevents their differentiation into adipocytes
multiple extracellular signals act in concert to regulate ________, and they intersect at the master gene encoding ______
adipogenesis, PPAR-gamma
PPAR gamma induces expression of _/___ which…
C/EBP alpha
Makes more PPAR gamma
Which stem cells give rise to progenitor cells for adipocytes
Mesenchymal stem cells
