Chapter 17: Cell Signaling Flashcards

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1
Q

what are the 4 steps in cell signaling?

A
  1. ligand/receptor binding
  2. activation of signal transduction
  3. relay of signal to the interior of the cell
  4. cellular responses/changes in gene expression
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2
Q

what are the 2 modes of cell signaling?

A
  1. direct cell-to-cell-signaling
  2. signaling by secreted molecules
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3
Q

explain direct cell-to-cell signaling

A

direct interaction of a cell w/ its neighbor or the cell matrix

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4
Q

what type of cell signaling is important in early development?

A

direct cell-to-cell

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5
Q

what are the 3 types of signaling by secreted molecules?

A
  1. endocrine signaling
  2. paracrine signaling
  3. autocrine signaling
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6
Q

describe endocrine signaling

A
  • signaling molecules are secreted by specialized endocrine cells & carried through the circulatory system
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7
Q

endocrine signaling acts on target cell at

A

distant body sites

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8
Q

what is an example of endocrine signaling molecule

A

hormones

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9
Q

describe paracrine signaling

A

signaling molecules act locally & affect the behavior of nearby cells

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10
Q

what is an example of a paracrine signaling molecule?

A

neurons via neurotransmitters

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11
Q

describe autocrine signaling

A

cells respond to their own signaling molecules

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12
Q

what is an example of an autocrine signaling molecule?

A

T lymphocytes & cancer cells

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13
Q

what are the 2 types of signaling molecules?

A
  1. non-surface receptor-binding ligands
  2. cell surface receptor ligands
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14
Q

give some examples of non-surface receptor-binding ligands

A
  • steroid hormones
  • thyroid hormone
  • retinoic acid
  • vitamin D3
  • nitric oxide
  • carbon monoxide
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15
Q

steroid hormones are synthesized from

A

cholesterol

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16
Q

steroid hormones are VERY

A

hydrophobic

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17
Q

give 3 examples of steroid hormones

A
  1. sex steroids
  2. mineralocorticoids
  3. corticosteroids
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18
Q

give 3 examples of sex steroids

A
  1. testosterone
  2. estrogen
  3. progesterone
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19
Q

what is an example of corticosteroids

A

glucocorticoids

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20
Q

what is considered to be a very important signaling molecule?

A

nitric oxide

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21
Q

steroid hormone receptors are typically found on the

A

inside of the cell

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22
Q

with non-surface receptor-binding ligands, after the intracellular receptors bind to the ligands they

A

diffuse across the membrane

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23
Q

what are the 4 main examples of cell surface receptor ligands

A
  1. neurotransmitters
  2. peptide hormones
  3. growth factors
  4. eicosanoids
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24
Q

give 5 examples of a neurotransmitter

A
  1. acetylcholine
  2. dopamine
  3. epinephrine
  4. serotonin
  5. GABA
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25
Q

give 7 examples of a peptide hormone

A
  1. insulin
  2. glucagon
  3. prolactin
  4. oxytocin
  5. FSH
  6. growth hormone
  7. neuropeptides
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26
Q

give 8 examples of GFs

A
  1. NGF
  2. neurotrophins
  3. BDNF
  4. EGF
  5. PDGF
  6. TGF-B
  7. FGF
  8. VEGF

BDNF: brain derived neutrophic factor

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27
Q

eicosanoids are similar to steroids but they

A

bind to surface receptors

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28
Q

give 2 examples of eicosanoids

A
  1. prostaglandins
  2. leukotrienes
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29
Q

what is the function of leukotrienes

A

inflammatory response by COX-1 and COX-2

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30
Q

what are the 5 major types of cell surface receptors?

A
  1. G protein-coupled receptors (GPCRS)
  2. ion channel receptors
  3. receptors w/ intrinsic enzyme activity
  4. receptor protein tyrosine kinases
  5. cytokine receptors & nonreceptor protein-tyrosine kinases (NrPTKs)
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31
Q

explain GTP-binding

A

the binding of a ligand activates a G protein

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32
Q

describe the 3 steps in GPCRs

A
  1. GTP-binding
  2. G protein activates enzyme
  3. catalyzes the synthesis of a second messenger
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33
Q

what second messengers are generated from the effector enzyme?

A
  • cAMP
  • inositol 145-triphosphate (IP3)
  • 1,2-diacylglycerol (DAG)
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34
Q

the effector molecule is on the

A

cytosolic side of the membrane

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35
Q

GPCRs have ____ transmembrane alpha-helices

A

7

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36
Q

G-protein is a

A

heterotrimer

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37
Q

to what subunit does GTP bind to on the G-protein?

A

alpha subunit

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38
Q

why can g-protein activate 2 things at once?

A

b/c the alpha subunit dissociates from the gamma & beta subunits

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39
Q

how does the G protein become inactive

A

by hydrolyzing the bound GTP to GDP

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40
Q

after the G-protein hydrolyzes GTP to GDP the subunits

A

recombine to form the inactive G-protein

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41
Q

the activation of adenylyl cyclase occurs through

A

binding of a hormone which in turn activates a G-protein

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42
Q

the hormonal activation of adenylyl cyclase occurs through a

A

GPCR

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43
Q

what are the functions of adenylyl cyclase?

A
  • generates cAMP by cleaving two phosphates off of ATP
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44
Q

how is a ion channel opened?

A

by ligand binding which triggers a conformational change

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45
Q

what causes the opening of additional ion channels?

A

membrane depolarization

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46
Q

when ion channels close the ligand is

A

degraded or recycled

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47
Q

in receptors with intrinsic enzymatic activity the cytosolic domains typically have

A

catalytic activity

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48
Q

some receptors with intrinsic enzymatic activity are monomers w/

A

guanylyl cyclase activity

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49
Q

some receptors with intrinsic enzymatic activity form

A

dimers w/ tyrosine kinase activity

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50
Q

the receptors that form dimers with tyrosine kinase activity form

A

SH2 binding sites

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51
Q

receptors for many growth factors have

A

intrinsic protein-tyrosine kinase activity

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52
Q

ligand binding to receptor tyrosine kinases causes the formation of an… and phosphorylation of its

A
  • activated homodimer
  • own cytosolic domain & substrate proteins
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53
Q

the receptor for epidermal growth factor (EGF) is typically a

A

receptor tyrosine kinase

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54
Q

the receptor tyrosine kinase is typically

A

1 transmembrane segment

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55
Q

what portion of the receptor tyrosine kinase binds the ligand?

A

the extracellular portion

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56
Q

the receptor tyrosine kinase has a series of _________ residues that are _________ for the _____________ __________.

A
  • tyrosine
  • substrates
  • tyrosine kinase
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57
Q

binding of second messenger (EGF) to a receptor tyrosine kinase causes receptor

A

aggregation & clustering

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58
Q

receptor tyrosine kinase ______________ each other at multiple tyrosine residues

A

cross-phosphorylate

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59
Q

what on the receptor tyrosine kinase creates binding sites for downstream molecules?

A

tyrosine phosphate residues

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60
Q

formation of phosphotyrosine residues on the receptor creates binding sites for downstream signaling molecules that contain

A

SH2 domains

SH: Scr homology

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61
Q

what is the ligand for Ca2+ channels in the ER

A

InsP3

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62
Q

list the 4 steps in NrPTKs

A
  1. ligand binding forms homo/heterodimer
  2. triggers activation of cytosolic protein-tyrosine kinase
  3. activated kinase phosphorylates tyrosine in receptor
  4. substrate proteins bind phospho-tyrosine residues & become phosphorylated
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63
Q

the cytokine receptors have NO

A

intrinsic enzymatic or catalytic activity

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64
Q

what functions in association with NrPTKs?

A

cytokine receptors

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65
Q

the cytokine receptors do not respond to _______ they only respond to _____.

A
  • GF
  • cytokines
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66
Q

what are the 2 kinase families seen in cytokine receptors

A
  • Janus kinase (JAK)
  • Src family (Rous sarcoma virus )
67
Q

binding of integrins to the ECM leads to

A

dimerization

68
Q

what is activated by autophosphorylation in integrin signaling?

A

NrPTK FAK (focal adhesion K)

69
Q

in integrin signaling Src binds to

A

FAK phospho-tyrosines

70
Q

Src phosphorylates FAK on additional tyrosine residues to have them

A

act as binding sites for downstream signaling molecules

71
Q

TGF-beta receptor family proteins are known as

A

protein serine-threonine receptor kinases

72
Q

type I and type II receptors only bind

A

TGF-beta

73
Q

binding of the GF to serine-threonine receptors results in

A
  • clustering of type I & type II receptors
  • phosphorylation by type II receptors
74
Q

the activated type I receptors phosphorylate

A

Smads

75
Q

Smads then bind to

A

co-Smads and enter the nucleus

76
Q

what are the 4 pathways of intracellular signal transduction?

A
  1. cAMP pathway
  2. phospholipids & Ca2+
  3. Ras, Raf, MAP Kinase Pathway
  4. JAK/STAT Pathway
77
Q

define signal transduction

A

the cascade of sequential reactions (greatly amplifies the signal)

78
Q

in signal transduction the binding of 1 molecule of epinephrine induces the synthesis of

A

many cAMP

79
Q

an increase in the steps of signal transduction leads to a greater

A

signal amplification potential

80
Q

β- adrenergic receptor is ONLY activated by

A

epinephrine

81
Q

α-adrenergic receptor is activated by both

A

epinephrine & norepinephrine

82
Q

what pathway is initiated by the activation of the β-adrenergic receptor

A

the cAMP pathway

83
Q

what pathway is initiated by the activation of the α-adrenergic receptor

A

inositol-phospholipid-calcium pathway

84
Q

phospholipase C cleaves

A

PIP2

85
Q

what is the function of PIP3?

A

acts as the 2nd messenger ligand for Ca2+ channels of the ER

86
Q

after PIP3 is cleaved what remains in the membrane?

A

diacylglycerol (DAG)

87
Q

DAG also acts as a __________ and is recognized by…

A

2nd messenger

protein kinase C

88
Q

what is an example of a cyclic nucleotide?

A

cAMP

89
Q

cAMP is synthesized from ________________ by….

A
  • ATP
  • adenylyl cyclase
90
Q

cAMP is degraded to __________ by…

A
  • AMP
  • cAMP phosphodiesterase
91
Q

cAMP-dependent Protein Kinase A (PKA) is a

A

tetramer

92
Q

cAMP-dependent PKA is composed of what subunits?

A
  • 2 regulatory
  • 2 catalytic
93
Q

cAMP binds to the… and causes them to

A
  • regulatory subunits
  • dissociate
94
Q

activated catalytic subunits of cAMP-dependent PKA phosphorylates

A

serine residues on target molecules

95
Q

PKA phosphorylation activates a number of important

A

metabolic enzymes

96
Q

what is the function of glycogen phosphorylase

A
  • glycogen breakdown
97
Q

what is the function of glycogen synthase

A

inhibits glycogen production

98
Q

an increase in cAMP initiates transcription of target genes that have a specific regulatory sequence…what is the name of these target genes?

A

cAMP response element (CRE)

99
Q

the catalytic subunit of PKA enters the nucleus and phosphorylates what transcription factor

A

CRE binding protein (CREB)

100
Q

the phosphorylation of CREB leads to the transcription of

A

cAMP inducible genes

101
Q

what removes the phosphates added to CREB by PKA ?

A

phosphatase 1

102
Q

the catalytic subunit of PKA requires what to get into the nucleus?

A

NLS

103
Q

receptor activated PKA phosphorylation is rapidly reversed by

A

protein phosphatases

  • terminate the response
104
Q

Pi-PLC stands for

A

phosphoinolsitol phospholipase C

105
Q

what stimulates the hydrolysis of PIP2 by PLC?

A

GF & hormones

106
Q

what are the byproducts of PI-PLC and PIP2?

A
  • DAG
  • IP3
107
Q

DAG stimulates the activation of

A

protein kinase C

108
Q

IP3 stimulates the release of

A

Ca2+ ions from ER

109
Q

Ca2+ is normally pumped into the

A

ER

110
Q

what binds to ligand-gated ion channels?

A

IP3

111
Q

DAG remains in the cell membrane to activate PKC family which is a family known for

A

cell growth

112
Q

in the PIP3/AkT pathway PIP2 is phosphorylated by

A

PI3-kinase

113
Q

PI3-kinase generates what second messenger?

A

PIP3

114
Q

PIP3 targets _____ and binds ________.

A
  • Akt
  • PDK1
115
Q

the activation of Akt requires what protein kinase

A

mTOR

116
Q

the PIP3/AkT pathway stimulates the activation of

A
  • Bad
  • transcription factors
  • GSK-3
117
Q

Bad is responsible for promoting

A

apoptosis

118
Q

why is the PIP3/AkT pathway known as a pathway with dual phosphorylation?

A

b/c it binds both PDK1 & mTORC2

119
Q

calmodulin is known as the major

A

Ca2+ binding protein

120
Q

CaM kinases phosphorylates a large number of

A
  • metabolic enzymes
  • ion channels
  • transcription factors
121
Q

CaM kinases are very abundant in the

A

nervous system

122
Q

calmodulin contains how many calcium binding sites?

A

4

123
Q

what is the target of calmodulin?

A

Ca2+/calmodulin-dependent kinase

124
Q

what are 5 methods of Ca2+ regulation in the cell?

A
  1. G protein-linked receptor
  2. Ca2+ channels
  3. Calcium Pump
  4. sodium-calcium pump
  5. ryanodine receptor channel
125
Q

once released from the ER Ca+ binds to

A

calmodulin

126
Q

what stimulates Ca+ release from the ER?

A

CCK or ACh

127
Q

an increase of Ca+ initiates what at the pancreatic duct

A

ZG fusion w/ cell membrane

128
Q

increase Ca+ triggers

A

CRAC channel opening

129
Q

In normal conditions when Ca+ is released what 2 steps proceed?

A
  1. trypsin activation in small intestine
  2. intestinal contents digested
130
Q

what occurs during the abnormal Ca2+ regulation in pancreatic acinar cells

A
  • excess Ca2+ released activates trypsin within ZGs
  • acinar cell/tissues begin to digest
131
Q

MAP Kinase stands for

A

mitogen-activated protein kinase

132
Q

what is known as a major pathway in cellular signaling that is highly conserved in eukaryotes?

A

MAP kinase pathways

133
Q

MAP kinases are composed of serine/threonine kinases that respond to

A

hormones/GFs

134
Q

MAP kinase pathways regulate

A

cell growth & differentiation

135
Q

what are the 2 families included in the MAP kinase pathways?

A
  • ERK
  • MEK
136
Q

Ras responds similarly to

A

α subunit of G-protein

137
Q

Ras was first identified as a

A

rat oncogenic protein caused by a virus

138
Q

Ras mutations in cancer cells results in a

A

continually active GTP-bound state

139
Q

what stimulates the exchange of GTP for GDP when activating Ras?

A

guanine nucleotide exchange factors (GEFs)

140
Q

what terminates Ras activity?

A

GTP hydrolysis

141
Q

the termination of Ras through GTP hydrolysis is stimulated by

A

GTPase-activating proteins (GAPs)

142
Q

what was the first evidence that the action of mutated genes can cause cancer?

A

Ras (rat sarcoma virus)

143
Q

what organizes the ERK & upstream activators of the MAP cascade?

A

scaffolding proteins

144
Q

what is an example of a scaffolding protein?

A

KRS

145
Q

KRS signaling cassette ensures the specific & efficient activation of

A

MEK -> ERK

146
Q

ERK dissociates from KSR and then

A

translocates to the nucleus

147
Q

JAK stands for

A

janus kinase

148
Q

STAT stands for

A

signal/transducers and activators of transcription

149
Q

STATs are a family of….. w/ ________ domains

A
  • 7 transcription factors
  • SH2 domains
150
Q

what recruits STATs

A

cytokine receptor stimulation

151
Q

STATs are translocated to the ___________ and stimulates…

A
  • nucleus
  • transcription of target genes
152
Q

what happens to the receptors for TGF-β after ligand binding?

A

type I & type II receptors associate

153
Q

how does phosphorylation of TGF-β receptors happen?

A

type II phosphorylates type I

154
Q

activated type I receptors in the TGF-β activate what specific types of proteins?

A

Smad

155
Q

Smads complex w/ other Smads & translocate to the nucleus where they regulate

A

gene expression

156
Q

TGF-β/Smad pathway is involved in

A

wound healing

157
Q

what are the 5 types of signaling networks?

A
  1. negative feedback
  2. positive feedback
  3. feedfoward relay
  4. stimulatory crosstalk
  5. inhibitory crosstalk
158
Q

explain a feedfoward signaling network

A

maintains pathway going & also effects downstream products

159
Q

explain the stimulatory crosstalk of a signal network

A

the product of one pathway stimulates the product of another pathway

160
Q

what is an example of crosstalk between pathways?

A

ERK & PI3-Kinase signaling pathways

161
Q

continue the flow ras/raf-> _________ -> __________

A
  • MEK
  • ERK
162
Q

continue the flow PI3-kinase -> _________ -> _________ -> ________

A
  • Akt
  • TSC2/TSC1
  • mTORC1
163
Q

Akt can also inhibit

A

Ras/Raf complex