Cell signaling pathways: growth factors Flashcards
what are growth factors
substances capable of inducing cell growth, proliferation, healing, and/or differentiation
what are the major types of growth factors
proteins and steroids
where do proteins bind
on surface of cell membrane
where do steroids bind
on cytoplasmic, nuclear receptors
what are the major families of growth factor receptors
tyrosine kinase activity, serine/threonine kinase activity, and GPCRs
what role do growth factors play in the body
embryonic growth, cell survival, and in wound healing in adults
what can the nerve growth factor (NGF) bind to
tropomyosin(TrkA) receptor or p75MTR
what are the effects of NGF binding to trkA
involved in neuronal differentiation and preventing cell death
what is the pathway for epidermal growth factor signaling
activation of EGFR leads to dimerization and recruitment of proteins like PLC and STAT transcription factors or PI3K binds with adaptor proteins. both of these pathways go to the nucleus to affect gene transcription
what are the 4 subfamilies of the TGF beta superfamily
-TGF beta subfamily
- decentaplegia (Dpp) related subfamily
-actin and inhibin subfamily
- fourth subfamily of diverse members
what is included in the decapentaplegic (Dpp) subfamily
BMPs and growth differentiation factors
what do activin and ibhibin subfamily of TGF beta superfamily do
regulate sex and organ development
what do proto-oncogenes do
encode growth factors and transcription factors to carry out normal growth, proliferation and survival
how are the majority of growth factors translated
as a pro-form and then undergo proteolytic processing steps by members of the proprotein convertase family of enzymes
what is furin
a proprotein convertase
what is furin involved in
-neuronal innervation
-control of juxtacrine and paracrine signaling
- cartilage breakdown
- tumor metastasis
what happens in neuronal innervation the pro beta NGF is cleaved by furin
neuronal innervation and survival
what happens to pro beta NGF when it is not cleaved by furin
apoptosis
what happens in signaling when EDA-1 is cleaved by furin
paracrine signaling
what happens in signaling when furin does not cleave EDA-1
juxtacrine signaling
what happens in cartilage breakdown with furin
furin cleaves and leads to the degradation of cartilage proteins
what happens in tumor metastasis with furin
furin cleaves a protein and results in tumor metastasis
how is TGF beta synthesized and released
the precursor undergoes dimerization and cleavage that results in a small latent complex and a large latent complex. the large complex in stored in ECM through the binding of the RGD motif to integrins and active TGF beta is released
what happens when TGF beta binds to its receptor
they bind to a specific type 2 receptor subunit which recruits a type 1 subunit. this results in phosphorylation of the recruited type 1 receptor which then phosphorylates a receptor regulated SMAD protein in the canonical/classical pathway
what does the canonical/classical pathway do
initiates a SMAD dependent intracellular signaling cascade that activates or inhibits gene transcription
describe the active structure of TGF beta ligands
homo or heterodimers, two polypeptide chains linked by a single disulfide bond
describe the type 2 TGF beta receptor
a serine/threonine kinase
what do SMAD complexes bind to in TGF beta signaling pathway
co factors on DNA
what are the 4 steps in wound healing
-hemostasis
-inflammatory phase
- proliferative phase
-remodeling phase
what happens in hemostasis phase of wound healing
within minutes post injury, platelets aggregate at the injury site to form a fibrin clot to control bleeding
what happens in the inflammatory phase of wound healing
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
what happens in the proliferative phase of wound healing
angiogenesis, collagen deposition, granulation tissue formation, epithelialization, and wound contraction
what happens in the remodeling phase of wound healing
collagen is remodeled and realigned along tension force lines and cells no longer needed are removed by apoptosis
describe what happens in canonical BMP signaling
dimerization of receptor upon BMP binding and autophosphorylation which phosphorylates SMADs to move into nucleus to affect gene transcription
what does temporal and spatial restrictions of growth factors mean
GFs are expressed in different sites in tissue at different times
what is reciprocal induction
in tooth development growth factors jump back and forth from mesenchyme to ectoderm to build up structures in the tooth
what does TNF do and how
mediates death pathways by inducing caspases that induce apoptosis
what are treatment options of periodontal defects
bone grafts, enamel matrix derivative (EMD), platelet derived growth factor (PDGF) or platelet rich plasma (PRP)
what are some growth factors that can undergo mutations
BMPs, TGF beta, PDGF beta, IGF1RI, NGF
what is IBS caused by
overproduction of TNF alpha
what are the types of IBS
chron disease and ulcerative colitis
how is IBS treated
monoclonal antibodies, infliximab and adalimumab, which prevent TNF alpha from binding to its receptor
what is used to treat rheumatoid arthritis
antibodies against TNF alpha or etanercept (Enbrel)
what does etanercept (Enbrel) do
used in RA. it is a recombinant fusion protein between the TNF alpha receptor and the constant region of the IgG1 antibody which bind to TNF alpha to prevent its actions
what does myostatin do
inhibitory factor that regulates muscle mass
what growth factors play a role in embryonic development of the craniofacial region and teeth
TGF beta and BMPs
what is the important growth factor in wound healing
TGF beta
what are platelet alpha granules good for
they are a rich source of a variety of growth factors
how are growth factors activated
proteolytic fragmentation
what family does myostatin belong to
TGF-beta superfamily
what does TNF do
mediates death pathways by inducing caspases that induce apoptosis
