Final: Ch 16 PI, SerK, Hedgehog Flashcards Preview

Cellular and Molecular Biology > Final: Ch 16 PI, SerK, Hedgehog > Flashcards

Flashcards in Final: Ch 16 PI, SerK, Hedgehog Deck (72):
1

do phosphoinositide pathways have long-term effects on gene expression?

yes

2

phosphoinositide pathways end with a variety of kinases, especially....

protein kinase C (PKC)

protein kinase B (PKB)

3

PKC & PKB play key roles in what 2 things

cellular growth and metabolism

4

hormonal stimulation of some GPCR leads to activation of ________ C

phospholipase C (PLC)

5

what does PLC do after activation

cleaves PIP2 to generate the second messengers DAG and IP3

6

signaling via the IP3/DAG pathway leads to...

an increase in cytosolic Ca and activation of PKC

7

which isoform of PLC is activated by GPCRs

beta

8

which isoform of PLC is activated by RTKs and cytokine receptors?

gamma - contains SH2 domains

9

what do the SH2 domains of PLC-gamma do

bind specific phosphotyrosines on the activated receptors

positions the PLC close to PIP2, and PLC gets phosphorylated

10

recruitment of PI-3 kinase to activated receptors leads to synthesis of _ phosphorylated phosphatidylinositols

2

11

how does the PI-3 kinase RTK/cytokine receptor pathway work

PI-3 kinase recruited to membrane by binding SH2 domains to phosphotyrosine on the cytosolic domain of activated RTK/cytokine receptors

catalytic domain of PI-3 kinase close to phosphoinositide substrates

phosphorylates 3' carbon

12

what do the products of the PI-3 kinase pathway do

act as docking sites for signal transducing proteins so the signal is passed downstream

ex. cell division, prevent apoptosis

13

polyoma virus

DNA virus that transforms mammalian cells to uncontrolled growth

uses oncoprotein middle T

researchers discovered PI-3 kinase when studying middle T

14

protein kinase B (PKB)

serine/threonine kinase also called Akt

Also has a PH domain that binds to the 3-phosphates from PI-3

15

since the inositol phosphates are present on the cytosolic face of the membrane, binding recruits the ______ protein to the cell membrane

entire protein

16

following hormone stimulation (rise in PI 3-phosphates), what does PKB do

binds the membrane bound 3-phosphates via the PH domain (releases active catalytic site) and becomes localized at the plasma membrane

need two other kinases (PDK1 and PDK2 to be fully active)

17

PDK1 and PDK2

PDK1 is recruited to the membrane via binding of PH domain - eventually encounters PKB and phosphorylates a thr residue in the activation lip

PDK2 phosphorylates a serine not in the activation lip

18

once fully activated, PKB can...

dissociate from the membrane and phosphorylate target proteins within the cell

19

activated PKB can phosphorylate and inactivate ___-apoptotic proteins like ___

pro-apoptotic, Bad

short-term effect that prevents activation of an apoptosis pathway that leads to death

20

PKB and the Forkhead TF FOXO3a

PKB promotes survival of cultured cells by phosphorylating FOXO3a

this reduces the TF's ability to induce expression of many pro-apoptotic genes

21

the PI-3 pathway is negatively regulated by ____ _________

PTEN phosphatase

overexpression in cultured mammalian cells promotes apoptosis by reducing the level of the PI 3-phosphates and hence activation and anti-apoptotic effect of PKB

22

is the PTEN gene deleted in many types of advanced human cancers?

yes, contributes to uncontrolled growth b/c of elevated levels of PI 3-phosphates

23

inositol phosphate (IP) releases stores of ____

Ca2+

24

transforming growth factor B (TGF-B) superfamily and the transforming growth factor B receptor superfamily

receptor serine kinases and signaling molecules

phosphorylate and activate the Smads TFs that regulate growth and differentiation pathways

25

in unstimulated cells, the Smads are located in the ______, but when activated they move into the ________ to regulate transcription

cytosol, nucleus (via NLS)

26

the primary function of the 3 human TGF-B isoforms is to....

strongly prevent cellular proliferation

induce synthesis of proteins that inhibit the cell cycle

27

TGF-B prevents growth in both...

the secreting cell (autocrine signaling)

neighboring cells (paracrine signaling)

28

many animal cell types produce and secrete members of the TGF-B superfamily in an ________ form that is stored attached to cell-surface molecules or in the ECM

inactive form

release of the active form from the matrix by protease digestion or inactivation of an inhibitor

leads to a quick activation of signaling molecules already in place

29

how did researchers identify the receptor TGF-B1 bound to

radiolabeled purified TGF-B1 with iodine 125

Cross-linking

purification revealed 3 different receptors

30

what are the 3 TGF-B receptor proteins called

RI, RII, RIII

31

RIII (B-glycan)

most abundant TGF-B receptor

cell surface transmembrane proteoglycan

binds and concentrates mature TGF-B molecules near the cell surface to aid their binding to RII

32

RI and RI receptor proteins are _____ transmembrane proteins with ______/_______ kinases as part of their cytosolic domains

dimeric, serine/threonine kinases

33

RII exhibits constitutive ______ activity

kinase

34

binding of TGF B to RI and RII causes what

induction of complexes containing 2 copies of each RI and RII

RII phosphorylates serine and threonine residues in RI to activate RI kinase activity

35

3 types of Smads

R-smads (receptor regulated -- Smads2 and 3)

co-Smads (Smad4)

I-Smads (inhibitory Smads)

36

what does the MH1 domain of R-Smads contain

a nuclear localization signal that is hidden in the inactive form

phosphorylation of serines in R-Smads by RI allows binding of an importin to the NLS, which allows transport to the nucleus

37

within the nucleus, R-Smads are continuously being _________ by...

dephosphorylated by a nuclear phosphatase

38

______ feedback loops regulate TGF-B/Smad signaling

negative feedback loops

39

in most signaling pathways, the response to a growth factor or other molecule decreases with _____

time (desensitization)

40

which two cytosolic proteins downregulate TGF-B/Smad signaling

SnoN and Ski

block transcription activation by a bound Smad complex by deacetylating histones

makes cells resistant to growth-inhibitory effects of TGF-B

41

what are the Wnts and Hedgehogs?

evolutionarily conserved families of signaling proteins

play key roles in developmental pathways

induce expression of genes required for a cell to acquire a new identity or fate

42

similarities of Wnt and Hedgehog pathays 4 things

bind receptors that are like GPCR, but don't activate G-proteins

in resting state, key TFs are ubiquitinated and targeted for proteolytic cleavage

activation of each pathway involves disassembly of cytosolic protein complexes, deubiquitination, and release of an active TF

the kinase GSK3 is used

43

NF-kB pathway controlled by ubiquitination

an inhibitor of a TF is deactivated by ubiquitination

in resting state, the TF NF-kB is in the cytosol bound to an inhibitor

stress-inducing conditions cause deubiquitination and degradation of the inhibitor, allowing cells to activate gene transcription

44

another function of polyubiquitination other than signaling things for degradation by proteases is....

forming a scaffold to assemble a key signal transduction complex

45

Wnt signaling triggers the release of a TF from a ______ protein complex

cytosolic

46

proto-oncogene

a normal gene whose inappropriate expression promotes cancer

ex. Wnt-1

47

Wnt means

wingless

48

what does the Wnt pathway control

brain development

stem cells

development of osteoblasts

49

Wnt proteins are secreted extracellular signaling molecules that are modified by addition of a ______ group near their N-termini

palmitate (hydrophobic)

tethers Wnt proteins to the membrane, limiting their action to nearby cells

50

2 cell-surface receptors Wnt acts through

Frizzled (Fz) - 7 transmembrane helices and directly binds Wnt

co-receptor LRP - associated with Fz

51

B-catenin (vertebrates) / Armadillo (flies)

major players in Wnt signaling

acts as a transcriptional activator and membrane-cytoskeleton linker protein

52

Wnt pathway

Wnt binds to Fz and the LRP co-receptor

kinases phosphorylate LRP and Axin binds

phosphorylation of B-catenin is blocked, allowing it to accumulate

B-catenin translocates to the nucleus and binds to TF as a co-activator

53

Hedgehog (Hh) signaling relieves ______ of target genes

repression

54

the Hh pathway involves ______ of an intracellular complex containing a TF

disassembly

55

unlike Wnt, the Hh protein undergoes distinctive ___-_________ processing

post-translational processing

56

do the two Hh membrane receptors move between the plasma membrane and intracellular vesicles?

yes

57

what happens to cells that receive a high or small amount of Hh

high: turn on genes to form certain structures

low: turn on different genes to form different structures

58

morphogens

signals that induce different cell fates depending on their concentration in target cells

59

how is Hh formed

from a precursor protein with autoproteolytic activity

cholesterol and palmitoyl is added, making it hydrophobic to limit its diffusion in the membrane

60

Hh pathway in flies

Hh binds to Patched (Ptc) to stop inhibition of Smo

Smo moves to the membrane, gets phosphorylated

Ci (a TF) moves to nucleus and recruits CREB-binding activator protein to express target genes

61

primary cilium

a single immotile cilium

62

intraflagellar transport proteins (ITF)

move proteins and particles from the base of a cilium to the tip

63

Hh pathway in vertebrates

Hh binding triggers movement of Smo to the ciliary memb and the KIF7 motor protein up the microtubule to the ciliary tip

Gli (a TF) accumulates and is transported down the cilium and released into cytosol --> nucleus

64

degradation of an inhibitor protein activates the _____ TF

NF-kB TF

65

in the inactive state, the NF-kB TF is...

in the cytosol bound to an inhibitor

66

activation of the NF-kB signaling pathway involves what

ubiquitination and degradation of the inhibitor, releasing the TF

rapidly activated in mammalian immune system cells in response to bacterial or viral infection

67

toll like receptors NF-kB

activated when bacterial or fungal cell walls bind toll-like receptors on the cell surface

68

NF-kB pathway

kinase phosphorylates inhibitor of NF-kB, which gets ubiquitinated and degraded by proteasomes

nuclear localization signal in NF-kB dimer is revealed, and it is transported to nucleus

NF-kB activates many genes

69

what types of genes does NF-kB activate

those encoding cytokines and chemokines

causes immune cells to infiltrate the site of infection

70

depending on the specific E3 ubiquitin ligase, ubiquitin forms multiple types of ______ that have different structures and functions

polymers

71

polyubiquitin chains linked to activated IL-1 receptor forms a scaffold that...

brings the TAK1 kinase near I-kB kinase complex and phosphorylates it

Signal is transmitted this way

72

When is NF-kB pathway activated

In response to viral or bacterial infection

Stress