BIOB11H3 Lecture Notes - Map Kinase Kinase Kinase, Receptor Tyrosine Kinase, G Protein–Coupled Receptor

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Published on 21 Apr 2013
School
UTSC
Department
Biological Sciences
Course
BIOB11H3
Professor
First we will talk about a very conserved pathway called the MAP kinase cascade. Then we
will talk about pathway interactions and later we will talk about apoptosis.
Last time we talked about receptor tyrosine kinase this type of communication isn't the
only thing this category of receptors does. Many of them are involved in governing cell
cycle control, that is, governing cell division. When the appropriate signal comes in, it might
be in the form of a growth factor type of hormone and it gets together with its receptor and
this activates a couple of intermediates called RAS and RAF. Ultimately this activates the
MAP kinase cascade. The MAP kinase cascade for the most part deals with the commitment
of cells to cell proliferation.
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Figure 15 20 shows what to gets the pathway rolling towards cell division. The growth
factor comes in and binds to a receptor if it exists. The usual thing takes place, trans auto
Phosphorylation occurs and the receptor is then phosphorylated. Then it interacts with
something else. * Change “several adapters” to one particular adapter called GRB2. GRB2
forms a complex as a sort of sandwich between an activator receptor, a molecule called SOS
and SOS relays the signal to this protein that is very important called Ras which is a
monomeric G protein. Just like the other G proteins that were heterotrimers this one
cannot be active unless it is bound to GTP.
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Figure 15 17 shows one of the ways that a ligand bound to its receptor can interact by
means of an adapter protein, GRB2. Here is the sandwich between the receptor and SOS
which defines the function of GRB2. SOS is a member of the family of proteins called GEF
that is guanine nucleotide exchange factors which exchang GTP for GDP on the Ras G
protein. Ultimately, the ligand binding. that is the growth factor, is going to activate the
molecule called RAF through RAS.
At the top of figure 15 20, at step number 4 what happened is that RAS has become
activated and this then begins to initiate what is called the mitogen activated protein
kinase cascade or MAP kinase cascade. A mitogen is a generic term that stands for any
substance that stimulates mitosis. What happens first is that this protein called RAF is
activated and as you can see it will enlist a kinase that has a target protein called MEK
which it is going to phosphorylate and become active as a kinase and phosphorylate a
protein called ERK and make it active. ERK in the phosphorylated form is referred to as the
map kinase MapK. The kinase that activates it is known as the map kinase kinase MapKK.
And the kinases that activates it is known as the map kinase kinase kinase MapKKK. Several
phosphorylation steps take place and in the end we have an active map kinase which
moves to the nucleus.
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Document Summary

First we will talk about a very conserved pathway called the map kinase cascade. Then we will talk about pathway interactions and later we will talk about apoptosis. Last time we talked about receptor tyrosine kinase this type of communication isn"t the only thing this category of receptors does. Many of them are involved in governing cell cycle control, that is, governing cell division. When the appropriate signal comes in, it might be in the form of a growth factor type of hormone and it gets together with its receptor and this activates a couple of intermediates called ras and raf. The map kinase cascade for the most part deals with the commitment of cells to cell proliferation. Figure 15 20 shows what to gets the pathway rolling towards cell division. The growth factor comes in and binds to a receptor if it exists. Phosphorylation occurs and the receptor is then phosphorylated.

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