Final: Ch 16 Notch/Delta, SREBP, Integration

Question 1

MMP

Answer 1

matrix metalloprotease

metal containing enzymes that cleave the extracellular segments of target proteins near the outer membrane

Question 2

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 ___

Answer 2

MMP, cytosolic, TF

Question 3

upon binding Delta, the _______ receptor is cleaved and releases a component ___

Answer 3

Notch, TF

Question 4

are the receptor Notch and its ligand Delta single spanning transmembrane proteins found on the cell surface?

Answer 4

yes

Question 5

when Delta on one cell binds Notch on another cell what happens

Answer 5

activated Notch undergoes two cleavage events

these result in the Notch cytosolic domain being released and functioning as a TF

Question 6

2 cleavage events Notch undergoes

Answer 6

ADAM cleaves the extracellular segment of Notch

Secretase cleaves the cytosolic segment of Notch, which translocates to the nucleus

Question 7

Delta and Notch are initially equivalent, but _____ Delta on the target cell and ________ expression of Delta on the source cell

Answer 7

decreases, increases

Question 8

what is disintegrin

Answer 8

a protein domain that binds integrins and disrupts cell-matrix interactions

Question 9

lateral inhibition

Answer 9

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

Question 10

many signaling molecules are synthesized as transmembrane proteins whose signal domain extends into the _________ region… ex.

Answer 10

extracellular

ex. Delta

Question 11

many growth factors and other proteins are synthesized as transmembrane ______ whose cleavage results in….

Answer 11

precursors

cleavage releases soluble active signaling molecule into the extracellular space

Question 12

what class of protein are the ADAM family and what can heightened ADAM activity result in?

Answer 12

MMPs

increased activity is seen in cancers (high levels of EGF, destroys ECM to facilitate metastasis)

Question 13

inappropriate cleavage of amyloid precursor protein can lead to _________ disease

Answer 13

Alzheimer’s disease

amyloid plaques accumulate from cleavage ofamyloid precursor protein (APP)

Question 14

proteolysis of SREBP releases a __________ _______ that acts to maintain __________ and ________ levels

Answer 14

transcription factor, phospholipid, cholesterol levels

Question 15

LDL

Answer 15

low density lipoprotein

rich in cholesterol and transports it through the circulatory system

Question 16

both the cholesterol biosynthetic pathways and cellular levels of LDL receptors are ____-______ when cellular levels are adequate

Answer 16

down-regulated

Question 17

SRE-binding protein (SREBP)

Answer 17

cholesterol-dependent transcription factors

interact with sterol regulatory elements in the promoters to modulate expression of genes

Question 18

when cells have ______ cholesterol, SREBP is found in the ___ membrane complexed with SCAP, insig-1, and other proteins

Answer 18

adequate, ER membrane

Question 19

when cholesterol levels drop sufficiently what happens

Answer 19

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

Question 20

result of nuclear SREBP

Answer 20

expression of genes that import cholesterol into the cell (LDL receptor)

expression of genes that synthesize cholesterol like HMG-CoA reductase

Question 21

does SCAP recycle back to the ER?

Answer 21

yes

Question 22

what do statins do

Answer 22

reduce plasma LDL

bind HMG-CoA reductase to inhibit it

increase # of LDL import receptors in liver

Question 23

maintenance of blood glucose concentration depends on which two hormones

Answer 23

insulin (beta cells)

glucagon (alpha cells)

Question 24

insulin _______ the level of blood glucose

Answer 24

reduces

Question 25

glucagon ______ the level of blood glucose

Answer 25

increases

Question 26

what happens to blood glucose after a meal

Answer 26

raises above normal level, and pancreatic beta cells release insulin (binds receptors)

insulin binding insulin receptor tyrosine kinase activates protein kinase B

Question 27

what does protein kinase B do after it’s activated by insulin tyrosine kinase receptors

Answer 27

phosphorylates a target protein that triggers the rapid fusion of vesicles containing the glucose transporter GLUT4 with the membrane

this lowers blood sugar

Question 28

insulin stimulation of muscles cells does what…

Answer 28

enhances conversion of glucose into glycogen

PKB activates glycogen synthease

Question 29

insulin stimulation effect in liver cells…

Answer 29

inhibit glucose synthesis

Question 30

when blood glucose drops normally what happens

Answer 30

GLUT4 receptors are internalized and glucose import lowers

Question 31

if blood glucose drops too much what happens

Answer 31

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

Question 32

diabetes mellitus

Answer 32

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)

Question 33

multiple signal transduction pathways interact to regulate ________ differentiation through _____ the master transcriptional regulator

Answer 33

adipocyte, PPAR-gamma

Question 34

what are the major cells for storing fats

Answer 34

white adipocytes

Question 35

are adipocytes also endocrine cells that secrete signaling proteins?

Answer 35

yes

Question 36

PPAR-gamma

Answer 36

a transcription factor member of the nuclear receptor superfamily

master transcriptional regulator of adipocyte differentiation

Question 37

a knockdown of the gene for PPAR-gamma in preadipocytes does what

Answer 37

prevents their differentiation into adipocytes

Question 38

multiple extracellular signals act in concert to regulate ________, and they intersect at the master gene encoding ______

Answer 38

adipogenesis, PPAR-gamma

Question 39

PPAR gamma induces expression of _/___ which…

Answer 39

C/EBP alpha

Makes more PPAR gamma

Question 40

Which stem cells give rise to progenitor cells for adipocytes

Answer 40

Mesenchymal stem cells