9/20/21 Cell Signaling Pathways: Growth Factors Flashcards
What are growth factors?
- Substances capable of inducing cell growth, proliferation, healing and/or differentiation
- major types are proteins and steroids
- critical roles: embryonic development and repair processes of human tissues and organs.
Growth factor signaling involves what?
Signaling involves binding to a cell membrane receptor and then activation of various intracellular signaling pathways
what are the major families of growth factor receptors
with tyrosine kinase activity, serine/threonine kinase activity, and G-protein coupled receptors.
what are the 2 main nerve growth factor receptors?
- TrkA
2. p75 NTR
TrKA receptor role and goal
- facilitates receptor dimerization and tyrosine residue phosphorylation of cytoplasmic tail
- goal: activation of genes promoting survival
p75 NTR role and goal
- initiates NFkB and JNK
goal: activation of gene promoting survival and apoptosis
Epidermal Growth Factor Signaling
Activation of EGFR leads to homo/heterodimerization, phosphorylation of specific tyrosine residues, and recruitment of several proteins at the intracellular portion of the receptors.
TGF-β Superfamily and its 4 major subfamiles
One of the largest groups of cell regulatory proteins
- TGF-beta subfamily
- Decapentaplegic (Dpp) and growth differentiation factors
- Activin and inhibin subfamily (they regulate sex organ development)
- diverse members
what type of gene is for many growth factors or their receptors?
proto-oncogenes
do all proto-oncogenes encode transcription factors?
no, but many do
majority of growth factors are translated into what?
a pro-form and then undergo proteolytic processing steps of the proprotein convertase family of enzymes.
There are 9 members of the proprotein convertase family, which one is studied best?
furin
furin cleaves a number of proproteins. what are the 4 different ways?
- neuronal innervation
- control of juxtacrine vs. paracrine signaling
- cartilage breakdown
- tumor metastasis
neuronal innervation
furin cleavage of pro-B-NGF results to neuronal innervation & survival
NO furin cleavage->apoptosis
control of juxtacrine vs. paracrine signaling
furin cleavage of Eda-1 undergoes paracrine signaling to reach target cell
cartilage breakdown
furin cleavage-> active ADAMTS-4-> degradation of cartilage protein ->rheumatoid arthritis
tumor metastasis
furin cleavage of pro-MT1-MMP-> tumor metastasis
TGF-β synthesis (intracellular)
- TGF-β precursor
- Dimerization & cleavage
- Small Latent Complex
- Large Latent Complex
- Secretion
- Stored assoicated with extracellular matrix thru RGD motif binding to αv integrins
- Active TGF-β is released
how are TGF-β ligands active?
as homo- or heterodimers, two polypeptide chains linked by a single disulfide bond.
(They initially bind to a specific type II receptor subunit, which recruits a type I receptor subunit. )
Type II receptor of TGF-β
- serine/threonine kinase.
- binding of ligand results in the phosphorylation of the recruited type I receptor.
how does type I receptor of TGF-β act in canonical or classical pathway?
phosphorylates a receptor regulated SMAD protein.
canonical or classical pathway
to initiate a SMAD-dependent intracellular signaling cascade that activates or inhibits gene transcription
think SMAD as
TGF-β
what is a member of the TGF-β Superfamil?
Myostatin (GDF8)
