Signal Transduction
are characteristic facial features (large forehead, deep embedded eyes, and protruding chin) and less frequently, involvement of the renal system.
Reduced Notch-1 and -3 expression is implicated in CADASIL syndrome, a subtype of inherited aortic disease, described as cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.
Truncation mutations in Notch, leading to increased Notch signalling, are (rarely) involved in T cell acute lymphoblastic leukaemia. Mutations in Delta-like 3 (DLL3) leads to spondylocostal dystosis, with abnormalities including hemivertebrae and blocked vertebrae accompanied by deformities of the ribs which gives rise to breathing problems and opportunistic respiratory infections.17
Ras and Notch act in concert to determine cell fate in vulva development of C. elegans
As related in Chapter 12, the anchor cells of C. elegans present EGF (Lin-3) which binds the EGFR (Let-23) of the p6 cell and that this acts to determine the vulval cell phenotype. The vulval structure develops from precursor cells
FIG 22.17 Cross-talk between Notch and the JAK/STAT signal pathway.
Notch cooperates with STAT3 in the process of astrocyte differentiation. Nicd induces expression of Hes1, which facilitates STAT3 activation by acting as a platform that gathers both STAT3 and its kinase JAK2. The ensuing phosphorylation renders STAT3 transcriptionally active, through dimerization. This sequence of events gives rise to expression of GFAP, an intermediate filament component and marker for astrocyte differentiation.
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Notch
that take on three different fates (see Figure 12.11, page 331). The first is reserved for p6, but since the anchor cells may also make weak contact with p5 and p7, or EGF may be shed from the membrane and diffuse in the tissue, it is important that p6 can repress its neighbours’ routes of development. This occurs through Ras (Let-60)-mediated expression of Dsl-ligands (see Table 22.1) which in turn activates the Notch (Lin-12) pathway in both p5 and p7. The Notch signal blocks EGFR signalling in a number of ways so enabling the neighbouring p5 and p7 cells to adopt the second fate. Ras also prevents cell membrane expression of the Notch receptor (Lin-12) in p6 cells thus blocking a possible reciprocal action of p5 or p8.
For more information, see http://www.wormbook.org/
List of Abbreviations
Abbreviation |
Full name/description |
SwissProt entry |
Other names/OMIM |
|
|
|
|
achaete |
Drosophila, loss of macroand |
P10083 |
|
|
microchaete |
|
|
|
|
|
|
ADAM10 |
a disintegrin and metalloprotein |
O14672 |
Kuzbanian homologue |
|
domain containing protein-10 |
|
|
|
|
|
|
ADAM17 |
|
P78536 |
TACE |
|
|
|
|
a-adaptin |
AP2 complex αsubunit |
O95782 |
AP2A1 |
|
|
|
|
Apx-1 |
C. elegans, anterior pharynx in |
P41990 |
|
|
excess protein |
|
|
|
|
|
|
Arg-1 |
C. elegans |
Q17377 |
homolog of Notch |
|
|
|
|
armadillo |
|
P18824 |
segment polarity protein, b-catenin |
|
|
|
homologue |
|
|
|
|
CBF1 |
C-promotor binding factor-1 |
see CSL |
|
|
|
|
|
CPB |
CREB binding protein |
Q92793 |
histone acetyltransferase |
|
|
|
|
CSL |
CBF1 Su(H) Lag-1 |
Q06330 |
RBPJ |
|
|
|
|
Delta |
Drosophila |
P10041 |
neurogenic locus protein delta |
|
|
|
|
Delta-like 1 |
|
O00548 |
|
|
|
|
|
Delta-like 2 |
|
Q9NYJ7 |
|
|
|
|
|
Delta-like 3 |
|
Q9NR61 |
spondylocostal dystosis, |
|
|
|
MIM:277300 |
|
|
|
|
Deltex1 |
|
Q86Y01 |
|
Continued
727
Signal Transduction
Abbreviation |
Full name/description |
SwissProt entry |
Other names/OMIM |
|
|
|
|
Dishevelled-1 |
|
O14640 |
Dvl1 |
|
|
|
|
DSL |
delta serrate lag-2 |
|
|
|
|
|
|
DSL-1 |
C. elegans, DSL domain protein |
O45201 |
|
|
|
|
|
dynamin-1 |
|
Q05193 |
shibire homologue of dynamin |
|
|
|
|
E(spl)M3 |
Drosophila, enhancer of split-M3 |
Q01068 |
HLHm3 |
|
|
|
|
epsin1 |
|
Q9Y6I3 |
|
|
|
|
|
Fbw7/Sel10 |
F-box and WD domain |
Q969H0 |
archipelago homologue |
|
containing protein-7/suppressor |
|
|
|
encancer lin-10 |
|
|
|
|
|
|
fringe |
|
Q24342 |
O-fucosylpeptide 3-b-N- |
|
|
|
acetylglucosaminanyltransferase |
|
|
|
|
Frizzled |
|
Q9UP38 |
|
|
|
|
|
GFAP |
glial fibrillary acid protein |
P14136 |
intermediate filament component |
|
|
|
|
glp-1 |
C. elegans, germ line proliferation |
P13508 |
|
|
|
|
|
Groucho |
Drosophila, bushy eyebrows like |
P16371 |
|
|
Groucho Marx |
|
|
|
|
|
|
Hes1 |
hairy and enhancer of split |
Q14469 |
|
|
related protein1 |
|
|
|
|
|
|
Hey2 |
Hes with YRPW motif |
Q9UBP5 |
|
|
|
|
|
Id |
inhibitor of DNA binding-1 |
P41134 |
|
|
|
|
|
Itch |
itchy mice |
Q96J02 |
inflammatory skin disorder |
|
|
|
|
Jagged1 |
|
P78504 |
MIM 118450 Alagille syndrome |
|
|
|
|
Jagged2 |
|
Q9Y219 |
|
|
|
|
|
JAK2 |
Janus kinase-2 |
O60674 |
|
|
|
|
|
LAG-2 |
C. elegans |
P45442 |
longevity-assured gene |
|
|
|
|
lin-12 |
C. elegans, abnormal cell |
P14585 |
|
|
lineage-12 |
|
|
|
|
|
|
Mam |
mastermind |
Q92585 |
|
|
|
|
|
Mam |
Drosophila, mastermind |
P21519 |
neurogenic protein |
|
|
|
|
Continued
728
Notch
Abbreviation |
Full name/description |
SwissProt entry |
Other names/OMIM |
|
|
|
|
MIB1 |
mind bomb-1 |
Q86YT6 |
|
|
|
|
|
MyoD1 |
myoblast determination protein |
P15172 |
myogenic factor-3 |
|
|
|
|
NEDD4 |
neural precursor cell expressed |
P46934 |
|
|
developmentally down reg. 4 |
|
|
|
|
|
|
neuralized-like |
|
O76050 |
|
|
|
|
|
Notch |
Drosophila, notched wing |
P07207 |
|
|
|
|
|
Notch1 |
notched wing |
P46531 |
Translocation associated notch |
|
|
|
protein TAN1, MIM:187040 |
|
|
|
|
Notch2 |
notched wing |
Q04721 |
alagille syndrome, MIM:125310 |
|
|
|
|
Notch3 |
notched wing |
Q9UM47 |
CADASIL syndrome, MIM:25310 |
|
|
|
|
Notch4 |
notched wing |
Q99466 |
INT3 oncogene |
|
|
|
|
Numb |
deprived of feeling |
P49757 |
involved in sensory organ |
|
|
|
development |
|
|
|
|
p300 |
protein of 300 kDa |
Q09472 |
histone acetyltransferase |
|
|
|
|
POFUT1 |
peptide O-fucosyltransferase-1 |
Q9H488 |
|
|
|
|
|
Presenilin1 |
|
P49768 |
PSEN1 |
|
|
|
|
Rab11A |
Ras-related in brain-11A |
P62491 |
|
|
|
|
|
Rab5A |
Ras-related in brain-5A |
P20339 |
|
|
|
|
|
Rab7A |
Ras-related in brain-7A |
P51149 |
|
|
|
|
|
RBP-Jk |
recombination signal sequence |
see CSL |
|
|
binding protein for Jkappa |
|
|
|
|
|
|
scute |
Drosophila, scutellars on |
P10084 |
|
|
mesonotum |
|
|
|
|
|
|
Serrate |
Drosophila |
P18168 |
|
|
|
|
|
SIRT1 |
silent information regulator-like |
Q96EB6 |
sirtuin family of NAD-dependent |
|
protein-1 |
|
deacetylases |
|
|
|
|
SKIP |
ski interacting protein |
Q13573 |
SNW1, homologue of Drosophila |
|
|
|
Bx42 |
|
|
|
|
Smad1 |
sma mothers against |
Q15797 |
|
|
decapentaplegic-1 |
|
|
|
|
|
|
Continued
729