Receptor Tyrosine Kinases
by MikeGeneLet's talk about receptor tyrosine kinases (RTKs). We can think of an RTK as a communication device, since these membrane proteins transmit signals from the cell's environment into the cell. Event X outside the cell is translated into Event Y inside the cell. Specifically, the signaling molecules (such as hormones) bind the extracellular portion of the receptor protein. This binding event is then somehow communicated to the contents inside the cell. But how?
The RTKs span the membrane only through a single alpha helix, which means that you probably can't transmit a conformational change from the external part of the protein to the internal part. Instead, the transmission strategy employs dimerization, where two RTKs bind to a signaling molecule which in turn leads the two RTKs to stick to each other.
Once they are stuck to each other, we can shift our focus to the part of the RTK that is under the membrane and exposed to the cell's cytoplasm. The cytoplasmic components of each RTK now attach phosphate groups to each other (phosphates are added to the amino acid tyrosine). Once this happens, they become docking and activation sites for a variety of intracellular signaling proteins. These activated intracellular proteins can then kick off a cascade of events that can spread and/or amplify the signal, resulting in dramatic changes in the cell's metabolism or gene expression. Of course, if you can turn on a switch, you better have a way turn off the switch, so your cells also possess protein tyrosine phosphatases that can strip the phosphates off the receptor's tyrosines when needed.
Thus, RTKs can couple two seemly unrelated events "“ the binding of some molecule to the outside portion of the receptor and phosphorylation of the inside part of the protein. The latter event is a common way for cells to turn things ON and OFF, meaning that the binding of some molecule on the surface of the cell can radically alter what happens inside the cell. The modularity of this strategy is essentially conventional, where the relationship between the signaling molecule and intracellular events is determined solely by the identity of the binding domain of the RTK and the identity of the intracellular molecules that become activated by the RTK. If you swap extracellular binding domains, for example, it would simply mean that a different signaling molecule could elicit the same response. Such a process would clearly facilitate multicellular life, as signaling molecules released from one type of cell in your body would control the activity of a cell in another part of your body. And the potential for permutations needed to control a myriad of cells and processes is built into the basic design of this process.
We're now ready to crawl through another bunny hole….
March 23rd, 2008 at 9:07 pm
The signal transduction process appears to fit the meaning of irreducible complexity does it not? Any ideas as to how this function would have evolved?
Comment by Nathan — March 23, 2008 @ 9:07 pm
March 23rd, 2008 at 9:19 pm
You'd first have to define the IC players.
Comment by MikeGene — March 23, 2008 @ 9:19 pm
March 24th, 2008 at 2:51 pm
from - G-Proteins: The Molecular Swtiches
Nice post, Mike. I was looking forward to a follow up on the idea you started with your paper on G-proteins.
Comment by Doug — March 24, 2008 @ 2:51 pm
March 24th, 2008 at 10:46 pm
Ooh! I love membrane talks. The cellular membrane is, imo, a defeater of any theory of an a-biotic origin for life.
But what is the impact and effect of the cell membrane on subsequent evolution? The fact is that we live in a multi-cellular world.
It's not just that cells can sense their environment, but that they can at all "communicate" with each other!
What is the theory which accounts for this?
In the context of RTK's, Mike mentions hormones. But aren't hormones themselves proteins which are created within cells?
If so, then we need to reflect upon the following:
Why would a cell create a hormone?
Why would a passage exist for that hormone to exit the cell?
Why would some other cell create a passage by which that hormone could enter?
Why would that hormone have a meaning of any kind whatsoever within the receptor cell!?
Accident?
Do we have any evidence whatsoever that hormones which are produced within a cell have some "meaning or purpose" or function within the cell wherein they are produced?
From Wikipedia
For those of you who are interested, we can devise a "software development" analogy. But inheritance and chance have no meaningful role to play. Neither does "natural selection."
I'm absolutely amazed at what I find in the wiki article.
Cells which have their function regulated by other cells.
By definition, such cells must "express a receptor for the hormone."
But that does not even come close to an explanation of how that cell came to have it's "function" regulated by another cell!
Comment by Mung — March 24, 2008 @ 10:46 pm
March 24th, 2008 at 10:51 pm
MG, any online resources we can consult about these receptors and hormones? This is a fascinating subject!
I hope you'll not think me impertinent for asking for Design Matrix scores ;).
Or perhaps I am getting ahead of things.
Comment by Mung — March 24, 2008 @ 10:51 pm
March 24th, 2008 at 11:08 pm
Not necessarily.
To communicate.
Steroid hormones, for example, are lipids and thus don't need a passage to exit the cell.
Steroid hormones, for example, are lipids and thus don't need a passage to exit the cell.
To react to the communication.
No.
Yes.
PS: Funny that in your opinion the cellular membrane is a defeater of any theory of an a-biotic origin for life, yet you appear refreshingly ignorant on the topic of communication and transport across membranes.
Comment by hrun — March 24, 2008 @ 11:08 pm
March 24th, 2008 at 11:09 pm
Mung:
Good questions. Hormones are part of intricate, interactive systems among cells.
Comment by Bradford — March 24, 2008 @ 11:09 pm
March 24th, 2008 at 11:12 pm
Quick point, but I have to go to bed. A hormone is just one type of signaling molecule. For example, glucose can function as a signaling molecule. As for hormones, they don't need to be proteins. Many are simply modified amino acids. In fact, some amino acids function as neurotransmitters.
Comment by MikeGene — March 24, 2008 @ 11:12 pm
March 25th, 2008 at 6:33 am
hrun:
This is a funny reaction hrun. Since you are not ignorant, why not cite what knowledge of membrane communication and transport functions encourages a belief in abiotic origin theories?
Comment by Bradford — March 25, 2008 @ 6:33 am
March 25th, 2008 at 7:44 am
Bradford, I did not demonstrate my ignorance by asking numerous questions about hormones that are part of any entry level college textbooks and then use that lack of knowledge to proclaim that "the cellular membrane is, imo, a defeater of any theory [...]". Mung, apparently, has no problem doing so. That's what's funny.
Comment by hrun — March 25, 2008 @ 7:44 am
March 25th, 2008 at 3:28 pm
Kind of a cool article on an HIV protein that has an easy way to penetrate cell membranes.
The TAT protein, containing only 11 amino acids, is able to slip through the cellular membrane. Six of the 11 amino acids are the positively charged amino acid arginine.
The positively charged arginine is attracted to the negatively charged head of the hydrophilic portion of the lipid membrane. The attraction causes the membrane to deform slightly; creating pores 6 nanometers in diameter allowing for relatively easy access into the cell.
Stealthy HIV Protein
Comment by Doug — March 25, 2008 @ 3:28 pm
March 25th, 2008 at 6:45 pm
Before I go spelunking I need to know on which end of the bunny the hole is located. Where ya going with this?
If one alpha-helix cannot transmit, but two (dimerized) alpha-helices can transmit, then it is "irreducibly simple."
I'm sure I don't understand.
Comment by Rock — March 25, 2008 @ 6:45 pm