Lecture 3 - Signaling and Genetics of Craniofacial Development Flashcards
Importance of BMP 2 and BMP 7
They are FDA approved growth factors that can be given to bone defets. Will promote osteoblast differentiation
And Accelerate bone healing
TGF-Beta superfamily Consists of
Growth factors!! Three subfamilies BMP TGF-beta and Activin signal transduction path is similar
Potency of BMP?
Very potent so only seen in very small amount
What two things are required for Signal Transduction, and what is typically seen as the order
Requires - Protein -protein interaction
requires - post translational modification
Typically needs growth factor, receptor, signal transducer, transcription factor
Growth Factor Qualities
Usually bind with high specificity to membrane proteins
Binding results in a complicated cascade of secondary messengers that express transcription of certain genes
Signal Transducers
Molecules utilized for intracellular signaling from membrane to nucleus. Transmit information
They are information carriers
Smad in TGF/BMP signaling
signal binds to tyrosine kinase, dimerize, cross phosphorylate, and goes to phosphorylate the smad complex. Smad goes to nucleus for targeting gene expression
Other Examples of Signal Transducers in these paths MAP Kinase Signaling JAK/STAT signaling NF-kB signaling and Wnt Signaling
MAPK
JAK/STAT
IKK
GSK and Beta Catenin
Transcription Factors
molecules proteins which bind to DNA sequence to control transcription. Recruit RNA polym
activate or repress
Examples of TFs for the following paths
Smad - in TGF/BMP path
Jun or fos in MAP kinase signaling
NF-kb in NF-kB path
B catenin in wnt signaling
How Growth Factors are Controlled (after secretion from cell)
1) prodomain - attaching full protein to a inactive molcule (must be removed)
or
2) ECM binding protein sticks the growth factor bindding at the membrane
3) ECM antagonist - can cluster around it and inactivate it
Or
4) stored within the ECM
Growth Factor Pathway for TGF-B signaling
propeptide - makes a small latent complex (SLC)
latent TGF-Beta binding protein (LTBP) which makes a large latent complex with SLC becomes LLC
so the slc get attached and thus creates a large latent complex that must dissociate or hae exposure of binding region
Fibrillin, collagem are very important for GF control also
Where diseases affect craniofacial development
Marfan
LDS (loeys Dietz Syndrome)
FOP (fibrodysplasia ossificans progressive )
1) Fibrillin (ECM protein)
2) TGF-Beta Receptor, also we see a bifid uvula as a different thing
3) - BMP Receptor (subfam of TGF)
