Signaling Factor Overview
Biology 324, Spring 2021
Summarizing important information from Barresi & Gilbert’s Chapter 4, I present
here a broad overview of the major families of signaling proteins that commonly
come up in developmental pathways, their general signal transduction pathways,
and the class(es) of transcription factor proteins involved in the cell’s response.
Paracrine factors (up to one or two cell-diameters away;
close neighbors)
Hedgehog family (Figure 4.24)
Includes Hh, Shh (sonic), Ihh (Indian), Dhh (desert)
• The Patched protein normally inhibits the Smoothened protein’s
activity. However, binding of Hedgehog to Patched (its receptor)
results in inhibition of the inhibition of Smoothened, and so
Smoothened becomes active. The signal transduction downstream
from Smoothened gets complicated and is different in different
organisms, but the end result is that the Cubitus interruptus (Ci)
(verts Gli) protein moves into the nucleus and becomes an
active transcription factor.
Receptor Tyrosine Kinases (RTK) (Figure 4.20)
Platelet Derived Growth Factor (PDGF) Family
Fibroblast Growth Factor (FGF) Family
• FGFs / PDGFs bind to trans-membrane receptors that have tyrosine
kinase activity on their cytoplasmic side. Ligand binding
activates the receptors’ kinase activity. The receptors then
activate Ras proteins on the cytoplasmic side of the plasma
membrane, and then a cascade of cytoplasmic
serine/threonine kinases functions to activate a variety of
transcription factors, including those of the Elk family.
Wnt family (Figure 4.28)
Includes Wnt and Wg(wingless)
• Wnt binds to its receptor Frizzled, and this activates the Disheveled
protein. Activated Disheveled inhibits the GSK-3 kinase, and this
allows the b-catenin protein to move into the nucleus and
become an activating transcription factor.
Let’s also just note here that Wnt is a wild and crazy paracrine factor
and its binding to Frizzled can also affect the cytoskeleton and
intracellular Ca++ levels.
Transforming Growth Factor Beta family (Figure 4.30)
Includes TGF-bs, Activins, Bone Morphogenic proteins (BMPs), Vg1, Nodal,
Dpp
• TGF-b binds to two types of trans-membrane receptors, Type I and
Type II, forming a hetero-dimer. The Type I receptor has
serine/threonine kinase activity on its cytoplasmic side, and it
phosphorylates the Type II receptor. That phosphorylation
activates the Type II receptor’s kinase activity and it then
phosphorylates various Smad proteins in the cytoplasm (for
example Activin triggers Smad2 and 3 phosphorylation; BMP
triggers Smad1 and 5 phosphorylation). Different
phosphorylated Smads dimerize with Smad4, move into the
nucleus and form both activating and repressing
transcription factors.
Juxtracrine factors (requires cell:cell contact)
Notch, Delta/Serrate/LAG-2 (DSL) Family (Figure 4.37)
Both Delta and Serrate are trans-membrane proteins
• Either Delta or Serrate binds to Notch, a trans-membrane protein on
an adjacent cell. This activates a Notch-specific protease in the cell
expressing Notch that snips off part of Notch’s intracellular tail
(NICD; Notch Intracellular Domain). The NICD then moves to the
nucleus and acts as an activating transcription factor.