Cell Signaling Pathways: Growth Factors Flashcards
What are growth factors?
things that are capable of inducing cell growth, proliferation, healing, and/or differentiation
What are most growth factors?
proteins/peptides and steroids
How does signaling for protein/peptide growth factors start?
binding to cell surface receptors
Major families of growth factors receptors :
tyrosine kinase, serine/threonine kinase, and G protein coupled receptors
What are the 2 receptors that nerve growth factor binds to?
TrkA and p75NTR
TrkA signalling pathways
- Ras–> Raf –> MEK–> ERK
- PLC –> PI3 kinase
-do not need to know specific pathways, just know that there are 3-4 main pathways that it is able to go through
What is the main pathway from p75ntr
NF k B
-important for making bones
What are the 2 main receptors that epidermal growth factors bind to?
EGFR and HER-2-3-4 heterodimer receptor
What is pathway after epidermal growth factor binds to EGFR receptor?
-lead to activation of transcription factors that lead to cell survival and proliferation
What is pathway after epidermal growth factor binds to HER 2-3-4 receptor?
endocytosis pathway that activate cell survival and cyclin D1 control (Cell cycle control)
Genes for many growth factors or their receptors are…
proto-oncogenes
What does it mean if something is the pro form of something else?
it is the longer version and needs be cleaved before it is activated
-done by proprotein convertase
What is the best studied proprotein convertase?
furin
Cleaving of proprotein will allow what kind of cell signaling?
paracine
No cleavage of a proprotein will allow what kind of cell signaling?
juxtacrine
What does ADAMT-4 do?
causes degradation of cartilage in the joints
what cleaves the TGF-b superfamily proproteins ?
furin
Synthesis of TGF-b
-formation of TGF-b precursor
-dimerization and cleavage by furin
-stay associated with part cleaved off (small latent complex)
-bind to LTBP to form large latent complex
-move to the extracellular
What causes activation and release of TGF-b?
-acidic pH
-proteases
-thrombospodin-1
-integrin mediated activation
-ROS (reactive oxygen species)
What receptor does TGF-b bind to?
type II receptor (serine/threonine kinase)
-type 1 is then recruited and phosphorylated
-type 1 then phosphorylates SMAD protein
Conical pathway for TGF-b binding activates what?
SMAD pathway for regulated gene transcription
what does the SMAD-dependent intracellular signaling cascade do?
activates or inhibits gene transcription
What does myostatin do?
inhibit muscle growth
4 phases of wound healing:
-hemostasis: platelets aggregate at injury site to form fibrin clot to control bleeding
-inflammatory phase: bacteria and debris removed
-proliferative phase: angiogenesis, collagen deposition, granulation tissue formation
-remodeling: collagen remodeled realigned along tension force lines and cells no longer needed removed by apoptosis
What things can interfere with wound healing?
diseases, diabetes, venous/arterial disease, old age, and infection
Canonical BMP signaling:
BMP binds to BMPR1 and 2
-causes phosphorylation of SMAD1 and 5
-SMAD 4 joins and then they regulate gene expression
What is reciprocal induction?
signaling of tissues back and forth for the formation of very complex structures
-used to form the teeth
Formation of salivary gland:
start looking like a mushroom
-growth factors of mesenchyme and epithelia work together to form the invaginations and very complex structure
Is growth factor expression the same in every cell at all times?
no, changes based on time in development and type of cell being looked at
Do growth factors work independently?
no, many work together at one time to ensure that everything is forming correctly
If growth factor is turned on for too long, what can happen?
-there can be failure to move on to the next step in the sequence
-differentiate cells in the wrong place
What does tumor necrosis factor activation lead to?
activation of caspase cascade and apoptosis
Why are platelet-derived growth factors (PDGFs) important in dentistry?
being studied to see if they can be used as treatment for periodontal disease
When you hear autoimmune, what is usually involved?
TNF
Inflammatory bowl disease
-autoimmune
-TNF-alpha involved in chronic inflammation
-treatment is antibodies that block TNF-alpha from binding to receptor
Rheumatoid arthritis
autoimmune
-treatment: use antibodies that bind to TNF receptor or add decoy receptor to take all TNF alpha away
Beefy cow and kid have what?
deficiency in myostatin
What BMP mutation does Grace have?
bachydactyly (short ass thumbs)
what is dr. dallas’s favorite growth factor?
TGF-b
how are growth factors restricted?
temporally and spatially
