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Flashcards in 3 4 5 Cell Signaling Deck (79):
1

gap jxn transmit ___ signals

electrical

2

gap jxn 1/ link and 2/ fxns include

1/ cytoplasm of two neighboring cells
2/ rapid txmission of APs, diffusion of metabolites ( eg ATP) and second messengers (eg Ca2+)

heart, brain cells

3

membrane bound signaling molecules

like gap jxns but farther apart
contact-dependent - cells next to ea other
signaling molecule bound to PM of one cell and interacts directly with receptor of adjacent target cell

immune cells

4

communication by chemical signals - main steps

*major form of xfer of info*
multi-layered transduction process
release of signal by signaling cell
transfer of signal
detection by receptor
decoding of signal by target cell
activation of effector molecule
response

5

neurocrine signals

neurotransmitters
i.e. noradrenaline, acetylcholine
released from nerve terminals into synaptic cleft to communicate with other neurons or non-neurons

6

endocrine signals

hormones
i.e. adrenaline, insulin, steroids
made and released from endocrine cells
transported to blood to target organ/cell

7

paracrine signals

i.e. histamine
made and released from endocrine cells, travel very short distances to target organ/cell

8

autocrine signals

i.e. prostaglandins
signaling and target cell is the same (itself)

9

hydrophobic signals

i.e. steroid hormones
diffused through membrane

***activate nuclear transcription pathways (genomic pathway) via intracellular receptors***

initiation of GENE TRANSCRIPTION!

10

hydrophilic signals

i.e. most signals
cell impermeable
recognized by plasma membrane receptors

11

PM receptors have 2 main fxns

1/ detect incoming signal
2/ transmit signal to cell interior

12

binding of ligand to receptors is (4)

of high affinity
saturable
reversible
specific

13

ligand-gated (ionotropic) receptors

ion channels
fastest of all receptors
binding of the ligand opens the channel to ions due to a conformational change

combines receptor, transducer, and amplifier

e.g. nicotinic receptors, GABA receptors

14

ligand-gated receptor functions (2)

1/ alter membrane potential to regulate excitable cells
2/ alter intracellular Ca2+ concentrations

15

g protein coupled receptors (GPCRs)

receptors coupled to heteroTRIMERIC g proteins (GDP or GTP) that fxn as transducers

7 transmembrane receptors

16

examples of GPCRs (2)

muscarinic receptors
adrenergic receptors

17

GPCRs are inactive when

g protein attached to GDP

18

GPCRs are active when

g protein attached to GTP

19

receptor tyrosine kinases

enzyme is intrinsic to receptor
single membrane spanning receptors
***extracellular area binds the signal, causes dimerization of receptors and phosphorylation of receptor by intrinsic tyrosine kinase activity***
cytosolic area has enzyme activity that tranduces signal

20

signal transduction by GPCRs requires 3 membrane bound proteins

1/ receptor
2/ G protein
3/ amplifier

21

N terminus of the GPCR

ligand binding domain

22

C terminus of the GPCR

exposed to cytosol

23

GPCR stimuli (long list)

light
odors
tastes
ions
amino acids
amines
nucleotides
nucleosides
prostaglandins
lipids
peptides
proteins

24

when a GPCR is activated, this happens

GDP-a is released in exchange for GTP
a subunit detaches from B-gamma and attaches to GTP
so you are left with GTP-a and B-gamma

25

these 2 components of a GPCR can generate second messenger dependent cellular responses

GTP-a
Beta-gamma

26

active GTP-a is deactivated by

hydrolysis of GTP via GTPase that is intrinsic to the a subunit

leads to GDP-a + B-gamma (trimer formation)

27

4 types of G proteins

Gs
Gi
G1
G12

28

Gs amplifier

adenylyl cyclases (AC)
stimulation

29

Gs amplifier

adenylyl cyclases (AC)
stimulation
B1 and B2

30

Gi amplifier

adenylyl cyclases (AC)
inhibition
a2

31

Gq amplifier

PLC-B
stimulation
a1

32

acetylcholine has two types of receptors

nicotinic
muscarinic

33

acetylcholine ligand-gated receptor

nicotinic receptor

34

acetylcholine GPCR

muscarnic receptor

35

main second messengers (5)

cAMP
cGMP
IP3
DAG
Ca2+

36

second messenger AC/cAMP pathway

AC = membrane bound
activation generates cAMP from ATP
activated by Gs-a (GTP bound)
inhibited by Gi-a or Go-a (GTP bound)

37

Gs - AC increased - ____ second messenger

cAMP increased

38

Gi - AC decreased - ____ second messenger

cAMP decreased

39

Gq - PLC-B increased - ____ second messenger

IP3, DAG

40

Gq - PLC-B increased - ____ second messenger

IP3/Ca2+, DAG

41

hydrolysis of PIP2 by PLC leads to

DAG and IP3

42

PLC-gamma is activated by

tyrosine phosphorylated receptor kinases

43

upon hydrolysis of PIP2, DAG stays in the membrane and IP3 diffuses to the endo/SR to release _____

Ca2+
via binding to IP3 receptors

44

main fxn of DAG (result of second messenger PIP2) is to

activate protein kinase C

45

Ca2+ "on" mechanisms consist of (2 things)

1/ Ca2+ entry across plasma membrane
2/ Ca2+ release from intracellular stores

46

Ca2+ entry across PM is carried out by (2 things)

voltage gated channels
ligand gated channels

47

Ca2+ release from intracellular stores is carried out by (2 things)

IP3 receptors
ryanodine receptors

48

activation of CG results in generation of second messenger _____

cGMP from GTP

49

guanylyl cyclases are associated with (2 things)

membrane/particulate GC
cytosol/soluble GC

50

physiological activator of particulate GC (guanylyl cyclase)

natriuretic peptides

51

physiological activator of soluble GC (guanylyl cyclase)

nitric oxide (NO)

52

RGS proteins

regulators of g-protein signaling
terminate g-protein signaling

53

RGS proteins

"regulators of g-protein signaling"
***they terminate g-protein signaling***
they are GTPase activating (GAP), promoting GTP hydrolysis

54

termination of cAMP/cGMP signaling is done by

PDEs (phosphodiesterases)

55

cAMP is turned into 5'AMP by

PDE4
PDE1

56

cGMP is turned into 5'GMP by

PDE5
PDE1

57

small G proteins

monomeric G proteins
i.e. Ras and Rho

58

small G proteins are activated by

GPT exchange factors (GEFs)

59

small G proteins are turned off by

GAPs: GTPase activating factors

60

___ phosphorylate proteins

kinases

61

____de-phosphorylate proteins

phosphatases

62

these three amino acids participate in protein phosphorylation

serine
threonine
tyrosine

63

cAMP-dependent protein kinase (PKA)

serine/threonine kinase
inactive as a tetramer (2 regulatory subunits, 2 catalytic subunits)

64

____ binds to regulatory units of PKA to activate it

cAMP (2 cAMP molecules per regulatory subunit, so 4 cAMP molecules total)

65

(5) serine/threonine kinases

PKA: cAMP dependent protein kinase
PKG: cGMP dependent protein kinase
PKC: protein kinase C
caMK: Ca2+/calmodulin dependent protein kinase
MAPK/ERK: mitogen-activated protein kinase/extracellular signal related kinase

66

MAPKs

growth factors activate them
activated by phosphorylation of an upstream kinase
***leads to activation of transcription factors***

67

amplification

receptor--> G protein --> second messenger --> kinase --> phosphorylation

68

receptor tyrosine kinase

growth factor receptor
monomer, gets activated by dimerization

69

phosphorylation of receptor tyrosine kinases provides docking sites for a number of proteins containing SH2 domain or PTB domain, including ___ and ____

Grb2
PLC-gamma

70

___ attaches to Grb2

Sos protein (a GEF, activator of small G protein Ras)

71

___ activates Ras

Sos

72

activation of PLC-gamma and hydrolysis of PIP2 leads to

second messengers IP3 and DAG

73

Activation of PI3 kinase results in formation of ___

PIP3

74

RTKs have 2 jobs

1/ receptor (tyrosine kinase activity)
2/ recruitment of other molecules

75

this hormone is also a receptor tyrosine kinase

insulin

76

insulin receptor activates the

PI3K pathway via IRS (Insulin Receptor Substrate)

77

insulin receptor consists of

2 extracellular a chains and 2 transmembrane B chains (with intrinsic tyrosine kinase activity) connected by disulfide bonds

78

tyrosine kinases include (2)

growth factor receptor
insulin receptor

79

____ or ____ reverse phosphorylation

serine/threonine phosphatases or tyrosine phosphatases