Cell Signaling Pathways Growth Factors

Question 1

what are growth factors?

Answer 1

substances capable of inducing cell growth, proliferation, healing, and/or differentiation

Question 2

what are the major types of growth factors? (2)

Answer 2

proteins and steroids

Question 3

signaling of growth factors involves

Answer 3

binding to a cell membrane receptor and then activation of various intracellular signaling pathways

Question 4

what are the major families of growth factor receptors? (3)

Answer 4

tyrosine kinase activity
seine/threonine kinase activity
G protein coupled receptor

Question 5

nerve growth factor (NGF) signaling pathway

Answer 5

Binding interaction between NGF and the TrkA receptor facilitates receptor dimerization and tyrosine residue phosphorylation of the cytoplasmic tail by adjacent Trk receptors. Trk receptor phosphorylation sites operate as Shc adaptor protein docking sites, which undergo phosphorylation by the TrkA receptor. The Trk receptor complex recruits a second adaptor protein called growth factor-receptor bound protein-2 (Grb2) along with a docking protein called Grb2-associated Binder-1 (GAB1) (not shown). Subsequently, phosphatidylinositol-3 kinase (PI3K) is activated, resulting in Akt kinase activation.

Question 6

TrkA

Answer 6

tropomyosin receptor kinase A

Question 7

TrkA is a high affinity receptor involved in

Answer 7

neuronal differentiation and preventing cell death

survival genes

Question 8

p75

Answer 8

neurotrophin receptor

Question 9

p75 is raining expressed in early

Answer 9

neuronal development

promote apoptosis

Question 10

EGF signaling pathway

Answer 10

Signaling pathways and inhibitors of EGFR. Activation of EGFR leads to homodimerization/heterodimerization, phosphorylation of specific tyrosine residues, and recruitment of several proteins at the intracellular portion of the receptors. Phospholipase Cγ (pink) and STAT transcription factors (blue) bind directly to the receptor, whereas Ras/Raf/MAPK pathway (orange) and PI3K pathway (green) need several specific adaptor molecules (yellow). PI3K can also bind directly any of the erbB partners of EGFR heterodimers. Concomitantly, the activated receptors undergo endocytosis and follow two possible routes: lysosomal degradation or importin-mediated nuclear translocation. Once in the nucleus, EGFR can either behave as a proper transcription factor (for cyclin D1 up-regulation) or as coregulator of other gene transactivators. Both pathways result in nuclear activation of genes related with cell proliferation, survival, invasion, and metastasis. Two main strategies are available for EGFR kinase inhibition: mAb and small-molecule TKIs. mAbs act extracellularly, avoiding EGFR ligands binding, whereas TKIs compete with the ATP binding to the kinase domain of the receptor. DAG, 1,2-diacylglycerol; IP3, inositol 1,3,5-triphosphate; PLCγ, phospholipase Cγ; Erk-1, extracellular signal-regulated kinase-1; Erk-2, extracellular signal-regulated kinase-2; FAK, focal adhesion kinase; PKC, protein kinase C.

Question 11

TGFb subfamilies (4)

Answer 11

TGFb subfamily
decapentaplegic (Dpp, Drosophila) related subfamily including BMPs and growth differentiation factors
action and inhibit subfamily fourth subfamily of diverse members

Question 12

BMPs

Answer 12

bone morphogenetic proteins

Question 13

action and inhibin subfamily regulate

Answer 13

sex organ development

Question 14

genes for many growth factors or their receptors are

Answer 14

proto-oncogenes

Question 15

not all proto-oncogenes encode growth factors. many encode

Answer 15

transcription factors

Question 16

how are the majority of growth factors translated?

Answer 16

as a pro-form and then undergo proteolytic processing steps by members of the pro protein convertase family of enzymes

Question 17

how many members are there of the pro protein convertase family?

Answer 17

9

furin is the best studied

Question 18

dr. forsake has studied — for many years

Answer 18

SKI-1 (important for processing with SREBP)

Question 19

furin

Answer 19

cleaves a number of pro proteins

Question 20

Turin is involved in (4)

Answer 20

neuronal innervation
control of juxtacrine versus paracrine signaling
cartilage breakdown
tumor metastasis

Question 21

steps of synthesis of TGFb (7)

Answer 21

TGFb precursor
dimerization and cleavage
small latent complex
large latent complex moves from the cytosol to the ecm
stored associated with eco through binding of the RGD motif to alpha integrins
proteases cleave
TGFb is released

Question 22

TGFb ligands are active as

Answer 22

homo or heterodimers

Question 23

homo/heterodimer

Answer 23

two polypeptide chains linked by a single disulfide bond

Question 24

ligand binds to a type 2 receptor, which will

Answer 24

recruit a type 1 receptor subunit

Question 25

type 2 receptor is a

Answer 25

serine/threonine kinase

Question 26

binding of the ligand results in the

Answer 26

phosphorylation of the recruited type 1 receptor

Question 27

in the canonical or classical pathway, the type 1 receptor then phosphorylates a receptor regulated

Answer 27

SMAD protein

Question 28

how many type 1 receptors and type 2 receptors are there in mammals?

Answer 28

1: 7 2: 5

Question 29

the canonical or classical pathway serves to initiate a

Answer 29

SMAD dependent intracellular signaling cascade that activates or inhibits gene transcription

Question 30

myostatin

Answer 30

inhibitor of muscle growth

Question 31

growth factors and cytokines affecting various steps in wound healing include (6)

Answer 31

``` fibroblast migration/replication keratinocyte replication angiogenesis collagen synthesis collagense secretion monocyte chemotaxis ```

Question 32

why do dogs lick their wounds?

Answer 32

their saliva is rich in TGFb which starts the wound healing process

Question 33

wound healing

Answer 33

complex process in which skin or other tissue repairs itself after injury

Question 34

the classic model of wound healing can be divided into four sequential overlapping phases:

Answer 34

hemostasis inflammatory phase proliferative phase remodeling phase

Question 35

hemostasis

Answer 35

within minutes post injury, platelets aggregate at the injury site to form a fibrin clot which acts to control bleeding

Question 36

inflammatory phase

Answer 36

bacteria and debris are phagocytosed and removed from the wound site. factors are released that cause migration and division of cells involved in the proliferative phase

Question 37

proliferative phase

Answer 37

angiogenesis, collagen deposition, granulation tissue ormation, epithelialization, and wound contraction

Question 38

remodeling phase

Answer 38

collagen is remodeled and realigned along tension force lines and cells no longer needed are removed by apoptosis

Question 39

examples of disease states which can interfere with wound healing progression (4)

Answer 39

diabetes venous or arterial disease old age infection

Question 40

diabetic ulcers

Answer 40

diabetic wounds do not heal quickly, sometimes don't even realize they have a wound

Question 41

hemostasis involves

Answer 41

platelets

Question 42

inflammatory phase involves (3)

Answer 42

monocytes neutrophils macrophages

Question 43

proliferative phase involves (3)

Answer 43

fibroblasts endothelial cells keratinocytes

Question 44

remodeling involves

Answer 44

fibroblasts

Question 45

BMP segnalino involves

Answer 45

SMADs

Question 46

SMADs result in

Answer 46

regulation of gene expression

Question 47

how is growth factor expression restricted? (2)

Answer 47

temporarlly and spatially

Question 48

how was it shown that growth factor expression is temporally and spatially separated in craniofacial growth and development?

Answer 48

transgenic mice expressed the lac z gene which is regulated by a BMP4 receptor. wherever BMP4 is lac z is expressed, which stains embryos with a blue dye, which shows BMP4 expression in different regions (expressed at different times and spaces in development)

Question 49

fracture healing involves

Answer 49

spatial and temporal restricted expression of multiple BMPs

Question 50

growth factors often work in combination to achieve

Answer 50

complex structures of growth and differentiation

Question 51

salivary gland branching morphogenesis involves multiple

Answer 51

growth factors expressed spatially and temporally

Question 52

do all growth factors stimulate growth?

Answer 52

no

Question 53

TNF

Answer 53

tumor necrosis factor

Question 54

TNF mediates

Answer 54

``` death pathways (intracellular signaling events lead to change in gene expression and cell death via apoptosis ```

Question 55

what types of therapeutic options can be placed in the periodontal defect? (4)

Answer 55

bone grafts enamel matrix derivative (EMD) platelet derived growth factor (PDGF) platelet rich plasma (PRP)

Question 56

why are these substances used to treat periodontal defects?

Answer 56

they're packed with growth factors to stimulate growth

Question 57

why are these substances used to treat periodontal defects?

Answer 57

they're packed with growth factors to stimulate growth

Question 58

BMP2 mutation

Answer 58

brachydactyly type A2, mutation in 3'-regulatory element suggestive of a long range regulator of transcription

Question 59

BMP4 mutations (2)

Answer 59

microphthalmia, eye, brain, and digit developmental abnormalities orofacial cleft, microform cleft lip and cleft palate

Question 60

BMP15 mutation

Answer 60

ovarian dysgenesis 2, hypergonadotropic ovarian failure

Question 61

BMPR, type 2 mutation

Answer 61

pulmonary hypertension

Question 62

Loeys-Dietz syndrome

Answer 62

caused by a mutation in the TGF-β receptor-1 and TGF-βreceptor-2. Autosomal dominant mutation causing widely spaced eyes, cleft palate or bifid uvula, and aortic aneurysms

Question 63

Camurati-Engelmann disease

Answer 63

autosomal dominant mutation in TGF-b1 causing progressive diaphyseal dysplasia (hyperostosis and sclerosis of diaphyses of long bones)

Question 64

Colorectal cancer hereditary nonpolyposis

Answer 64

mutations in TGF-β receptor-2

Question 65

Arrhythmogenic right ventricular dysplasia 1

Answer 65

mutation in TGF-β3

Question 66

PDGF-beta- dermatofibrosarcoma protuberans

Answer 66

Due to genetic rearrangement, PDGF-beta is produced without its normal regulation giving rise to tumor formation

Question 67

IGF1Rl

Answer 67

mutation in IGF-receptor which causes resistance to IGF-1. Leads to intrauterine growth retardation and short stature

Question 68

NGF

Answer 68

hereditary sensory and autonomic neuropathy. Mutation causing loss of deep pain and temperature perception

Question 69

inflammatory bowel disease

Answer 69

chronic relapsing intestinal inflammation

Question 70

two kinds of inflammatory bowel disease

Answer 70

chrons disease | ulcerative colitis

Question 71

chrons and ulcerative colitis are both classified as

Answer 71

autoimmune diseases

Question 72

what plays a key role in chronic inflammation?

Answer 72

TNFa

Question 73

inflammatory bowel disease treatment

Answer 73

monoclonal antibodies, infliximab and adalimumab, which are directed against TNFa and prevent its binding to its receptor

Question 74

rheumatoid arthritis

Answer 74

chronic inflammation

Question 75

chronic inflammation can be treated with

Answer 75

an antibody against TNFa or other type of inhibitor

Question 76

etanercept (Enbrel)

Answer 76

recombinant fusion protein between the TNFa receptor and the constant region of the IgG1 antibody, which binds TNFa and prevents its cellular action