Signal transduction (cell to cell signaling) Flashcards
signals tell cell to…
- survive
- divide
- differentiate
- die
steps of signal transduction
- signaling molecule bind to receptor (receotion)
- transduction (relay molecules)
- response OR termination
- ex: TF –> gene expression
important transcription factors
- homeodomain-containing TF (Hox, Pax, Lim)
- helix loop helix TF
- zinc finger TF
What are homeodomain containg TFs
- distinctive DNA binding sequence preferences
- contribute to specificity in target genes and diversity in function among homeodomain proteins
example of homeodomain containing tf
- hexapeptide: Hox
- engrailed
- Paired: pax
- LIM
What are Hox TF
- pattern the anterior posterior body axis playing crucial role in segment specific organogenesis
- normal temporo-spatial limb and organ development
How are Hox TFs similar to combinatorial gene control
- diff hox genes control expression in diff segments
- order of genes in chromosome specifies order in time of their expression and where expressed spatially
Describe loss of function Hox TFs
- if a segment is KOed, the expression will be taken over by another segment…
ex: KO band of XIHbox1 expression… hindbrain will take over that area
Pax TFs
- important for developmental steps… regional specification
LIM TFs
- involved in tissue patterning and differentiation… specifically neural patterning (head development)
Helix-loop-helix transcription factors
- basic helix-loop-helix: MyoD (muscle pattern .. master regulator TF)
- forkhead: FOX
Zinc finger transcription factors
- zinc finger: sox, WT1, Kruppel
sox
- works together with other Tf’s
regulatory gene hierarchy
- cascade of gene expression (genes that encode TFs)
- gene products in each class control expression of genes in next class
- results in:
- stepwise organization of embryo… smaller and smaller regions until segmentation
- same gene function at different period of development or in diff organs
Genes that guide development are..
- conserved
- earliest stages of human development occur under less rigid genetic control
mutation of pax genes leads to…
- larger segments of regions
mutation in pax gene
- larger segmented regions
genetic hierarchy
- top to bottom
maternal effect genes
gap genes
pair rule genes
segment polarity genes
homeotic genes
one of the principal themes in contemporary cancer research is
- role of mutant forms of developmentally important genes in converting normal cells to tumor
signaling molecules and pathways
- paracrine factors : diffusion of inducers from one cell to another
- matrix: matrix of one cell induces change in another
- contact : contact between inducing and responding cells
paracrine factors
- fibroblast growth factors (FGF)
- related growth factors (EGF)
- TGF-B superfamily
- hedgehog
- Wnt (wingless)
antagonists of paracrine factors
- noggin (BMP)
- chordin (BMP)
FGF and TGF-B pathways
- know graph
Growth factor to RTK
- GF -> RTK -> Ras -> MAPK cascade
Describe FGF complexity
- same protein discovered in different contexts
- biologically can interact in different ways to do different things, despite being the same protein
TGF-B to TGF-B/Smad signaling pathway
see graph
hedgehog signaling pathway
- hedgehod inhibit patched
- patched inhibit smoothened
- smoothened activate Ci protein made activator (Gli)
- activates transcription
Wnt signaling pathway
- see figure
- Wnt activate frizzle
- frizzle activate disheveled
- DSh inhibits GSK3
- GSK3 inhibit B-catenin
- B-catenin activate transcription
Direct cell contact
- delta notch
- cadherin (homophilic)
- other cell-cell adhesion molecules
delta-notch
- direct contact cell signaling
- communication
- controls cell differentiation processes during embryo/adult life…
- dysregulated in cancer
- lunatic fringe
Where do you see delta-notch signaling
- gliogenesis
- left-right asymmetry determination
- somite function
lunatic fringe
- acts in golgi to modify notch and alter notch’s ability to bind to its ligand Delta
- established anterior boundary of somites
cell to cell adhesion molecules
- see figures
extracellular matrix signaling moelcules and pathways
- integrin:
- principal receptors used by animal cells to bind to extracellular matrix
- heterodimers and
- function as transmembrane linkers between the extracellular matrix and actin cytoskeletion
examples of how singlaing pathways are complex integrated cell processing pathways
- branch points for multiple responses
- cross talk; integration of multiple signals
- reciprocal communication/ induction
