Download S2.Cell Signaling-Signaling and gene expresssion

Cell Signaling Pathways – A Case Study Approach
L. Emtage, L. Bradbury, N. Coleman, D. Davenport, A. Dunning and J. Grew
Signaling and Gene Expression
SCF
Plasma membrane
Kit
Grb2 Sos (Ras GEF)
(adapter)
MI
Ras
GTP
Ras
(G protein)
GDP
RAF
(MAPKKK)
P
MEK
(MAPKK)
P
ERK
(MAPK)
P
C
T F BP
M
ITF
P
The figure above shows how a series of proteins form a signal transduction pathway. This
pathway transmits a cellular signal from the receptor tyrosine kinase (RTK) Kit on the
plasma membrane, through the cytoplasm, to the cell nucleus, where it alters gene
expression.
The Kit protein is expressed in embryonic germ cells (precursors to sperm and eggs),
hematopoietic stem cells (blood cell precursors), and melanoblasts. Melanoblasts are the
precursors to melanocytes and retinal pigment epithelial (RPE) cells. Melanocytes are
found not only in the skin (where they produce the skin coloring pigment melanin), but
also in the inner ear, where they help form an important epithelial barrier in the cochlea.
Retinal pigment epithelial cells are found in the eye.
The transduction molecules GRB2, SOS, Ras, Raf, MEK and ERK are very widely expressed;
they may be activated by many different RTKs, and they may activate many different
transcription factors. In contrast, the transcription factor MITF is expressed only in
melanoblasts.
Questions
1. What do you think would be the effect on embryonic development if there was a
complete (homozygous) loss of the Kit receptor? A complete loss of SCF? A complete
loss of MITF?
Cell Signaling Pathways – A Case Study Approach
L. Emtage, L. Bradbury, N. Coleman, D. Davenport, A. Dunning and J. Grew
2. Individuals with Waardenburg syndrome Type 2A often have a white forelock and
premature greying, unusual pigmentation of the iris, such as heterochromia iridis, and
hearing loss. Waardenburg syndrome is a congenital disorder, caused by dominant
loss-of-function mutations in a gene or genes in this pathway. Which gene or genes
above could be mutated to give rise to Waardenburg syndrome 2A? Explain your
answer.
3. Very pale pigmentation, such as found in Icelanders, is thought to be due to a
polymorphism in SCF. If you were trying to identify the polymorphism responsible,
would you sequence the coding region or the regulatory region of SCF first, and why?