Chapter 1 GF's and Receptors

Question 1

Role of Growth factors

Answer 1

stimulate activity of genes that are required for growth and division

Question 2

Non-growth activities of growth factors

Answer 2

migration, differentiation, synthetic capacity

Question 3

What produces EGF and TGF alpha

Answer 3

macrophages, epithelial cells, salivary glands, keratinocytes

Question 4

Receptors for EGF and TGF alpha contain what

Answer 4

intrinsic tyrosine kinase activity

Question 5

EGFR1 (ERB-B1)

Answer 5

transmembrane receptor located on surface of epithelial cells
binds EGF and TGF alpha
once bound, regulates cell proliferation and differentiation

Question 6

Mutations of EGFR1

Answer 6

can lead to lung, head, neck, breast, and brain cancers

Question 7

ERB-B2 (HER2)

Answer 7

overexpressed in breast cancers

Question 8

Epidermal growth factor (EGF) functions

Answer 8

mitogenic for keratinocytes and fibroblasts
stimulates keratinocyte migration
stimulates formation of granulation tissue

Question 9

Functions of TGF alpha

Answer 9

stimulates proliferation of hepatocytes

Question 10

Hepatocyte growth factor (HGF) production

Answer 10

aka scatter factor
produced by fibroblasts, mesenchymal cells, endothelium, and non-hepatocyte liver cells
synthesized as a precursor pro-HGF activated by serine proteases released at sites of injury

Question 11

What is the receptor for HGF?

Answer 11

MET
has intrinsic tyrosine kinase activity
overexpressed or mutated in renal tumors and thyroid papillary carcinomas

Question 12

HGF functions

Answer 12

enhances proliferation of hepatocytes
increases cell motility
causes tissue differentiation during development (morphogen)
enhances hepatocyte survival

Question 13

Platelet-derived growth factor (PDGF) isoforms

Answer 13

AA, AB, BB–>always ctive

CC, DD must be activated via proteolytic cleavage

Question 14

PDGF storage and release

Answer 14

stored in platelet granules and released when platelets are activated

Question 15

PDGF production

Answer 15

platelets, activated macrophages, endothelium, tumors, keratinocytes

Question 16

2 PDGF receptors

Answer 16

PDGFR alpha and beta

Question 17

PDGF functions

Answer 17

chemotactic for neutrophils, fibroblasts, and smooth muscle cells (recruitment after injury)
activates and stimulates proliferation of fibroblasts and endothelial cells
stimulates ECM protein synthesis

Question 18

Vascular endothelial growth factor (VEGF) production

Answer 18

mesenchymal cells

Question 19

Isoforms of VEGF

Answer 19

A, B, C, D, and PIGF (placental growth factor)

homodimeric proteins

Question 20

VEGF-A

Answer 20

major angiogenic factor after injury and for tumors

induces angiogenesis by promoting endothelial cell migration, proliferation, and formation of vascular lumen

Question 21

VEGF-B and PIGF

Answer 21

important for embryological vessel development

Question 22

VEGF-C/D

Answer 22

important for angiogenesis and lymphangiogenesis

Question 23

What is the most potent inducer for VEGF production?

Answer 23

hypoxia via hypoxia inducible factor (HIF-1)

other inducing factors at sites of injury are PDGF and TGF-alpha

Question 24

Receptors for VEGF

Answer 24

VEGFR-1,2,3 (RTK’s)

VEGFR-2 is found in the endothelium and is the most important for angiogenesis

Question 25

When is VEGF production targeted?

Answer 25

cancers, macular degeneration, retinopathy of prematurity, and diabetic macular edema anti-VEGF used in macular degeneration

Question 26

What can soluble versions of VEGF lead to?

Answer 26

preeclampsia

Question 27

VEGF functions

Answer 27

stimulates proliferation of fenestrated endothelial cells | increases vascular permeability

Question 28

Fibroblast growth factor (FGF)

Answer 28

associated with heparan sulface once released into the ECM and wait there for injury to occur

Question 29

FGF production

Answer 29

macrophages, mast cells, and endothelial cells

Question 30

FGF receptor

Answer 30

FGFR 1-4

Question 31

2 types of FGF

Answer 31

FGF-1: acidic | FGF-2: basic

Question 32

KGF/FGF-7

Answer 32

also a kerinocyte produced from fibroblasts stimulates keratinocyte migration, proliferation, and differentiation

Question 33

FGF functions

Answer 33

chemotactic and mitogenic for fibroblasts stimulates angiogenesis stimulates ECM protein synthesis for wound healing hematopoeisis development

Question 34

TGF-beta isoforms

Answer 34

1,2,3, but TGF-Beta 1 is the most widespread

Question 35

TGF-beta production

Answer 35

platelets, endothelium, mononuclear inflammatory cells, T cells, macrophages, keratinocytes, fibroblasts, smooth muscle cells

Question 36

Does TGF-beta require proteolysis to become active?

Answer 36

yes

Question 37

2 receptors of TGF-beta

Answer 37

TGF-beta receptor I and II have threonine/serine kinase activity cause activation of tumor factors called smads via phosphorylation activated smads-->smad4 heterodimer: allows for nuclear translocation for suppression/activation of DNA

Question 38

TGF-beta pleiotropic activity

Answer 38

can cause actions that contradict each other

Question 39

TGF-beta functions

Answer 39

drives scar formation | wound healing

Question 40

Scar formation via TGF-beta

Answer 40

stimulates production of collagen, fibronectin, proteoglycans, inhibit collagen degradation, increase tissue inhibitors of proteases (TIMPs)

Question 41

Wound healing via TGF-beta

Answer 41

chemotactic for leukocytes and fibroblasts stimulates ECM protein synthesis suppresses acute inflammation-->limits inflammatory response