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E. C. Bailey et al.
Both Ptc proteins appear to respond to Shh because Shh overexpression
in the skin induces higher levels of both ptc1 and ptc2, although the
induction of ptc2 is modest (Carpenter et al. 1998). Why are ptc2 and
Shh produced in the same cells? It may be that these epithelial cells are
responding to Shh in an autocrine fashion or that ptc2 levels are always
high in the follicular epithelia to restrict or concentrate Shh at the site of
secretion. Genetic studies in vertebrates may help elucidate the roles of
ptc2 in signaling.
12.3 Hh Signal Transmission
from the Cytosol to the Nucleus
12.3.1 Cytosolic Components of Dh Signaling
The transduction of Hh signaling from the cell surface to the nucleus
involves a host of unusual components and mechanisms. A significant
number of these cytosolic components have been identified genetically
in Drosophila (Table 1). In several cases, the genetic interactions have
been substantiated with biochemical studies. How Hh signaling regulates many of these proteins is not well understood, but recent studies in
Drosophila have identified several interactions critical for regulating
transmission of the Hh signal to the nucleus.
The cytosolic proteins Costal2 (Cos2), Fused (Fu), and Cubitus interruptus (Ci) form part of a large complex that may regulate Hh-mediated
gene expression (Robbins et al. 1997; Sisson et al. 1997). Cos2, a
kinesin-like protein, binds microtubules and is believed to tether Ci, the
major transcriptional regulator of Hh target genes, to the cytoskeleton
and away from the nucleus (Robbins et al. 1997; Sisson et al. 1997). Fu,
a putative serine-threonine kinase required for Hh signaling (Preat et al.
1990), associates with both Ci and Cos2. Activation of signaling is
proposed to release Ci from this complex so that it can enter the nucleus
and regulate gene expression (Robbins et al. 1997; Sisson et al. 1997).
How this happens is not yet clear. Hh signaling may inhibit Cos2
function, activate the Fu kinase, or antagonize Suppressor of Fused -
Su(fu) - a protein that associates with Fu and Ci to oppose Hh signaling
(Pham et al. 1995; Monnier et al. 1998). The full nature of interactions
E. C. Bailey et al.
Both Ptc proteins appear to respond to Shh because Shh overexpression
in the skin induces higher levels of both ptc1 and ptc2, although the
induction of ptc2 is modest (Carpenter et al. 1998). Why are ptc2 and
Shh produced in the same cells? It may be that these epithelial cells are
responding to Shh in an autocrine fashion or that ptc2 levels are always
high in the follicular epithelia to restrict or concentrate Shh at the site of
secretion. Genetic studies in vertebrates may help elucidate the roles of
ptc2 in signaling.
12.3 Hh Signal Transmission
from the Cytosol to the Nucleus
12.3.1 Cytosolic Components of Dh Signaling
The transduction of Hh signaling from the cell surface to the nucleus
involves a host of unusual components and mechanisms. A significant
number of these cytosolic components have been identified genetically
in Drosophila (Table 1). In several cases, the genetic interactions have
been substantiated with biochemical studies. How Hh signaling regulates many of these proteins is not well understood, but recent studies in
Drosophila have identified several interactions critical for regulating
transmission of the Hh signal to the nucleus.
The cytosolic proteins Costal2 (Cos2), Fused (Fu), and Cubitus interruptus (Ci) form part of a large complex that may regulate Hh-mediated
gene expression (Robbins et al. 1997; Sisson et al. 1997). Cos2, a
kinesin-like protein, binds microtubules and is believed to tether Ci, the
major transcriptional regulator of Hh target genes, to the cytoskeleton
and away from the nucleus (Robbins et al. 1997; Sisson et al. 1997). Fu,
a putative serine-threonine kinase required for Hh signaling (Preat et al.
1990), associates with both Ci and Cos2. Activation of signaling is
proposed to release Ci from this complex so that it can enter the nucleus
and regulate gene expression (Robbins et al. 1997; Sisson et al. 1997).
How this happens is not yet clear. Hh signaling may inhibit Cos2
function, activate the Fu kinase, or antagonize Suppressor of Fused -
Su(fu) - a protein that associates with Fu and Ci to oppose Hh signaling
(Pham et al. 1995; Monnier et al. 1998). The full nature of interactions