A Little Spiel on Her2Neu


by Van Warren

Her2Neu is a cell surface receptor. Think of it like a clove in an orange. Make that two cloves.


A cell surface receptor has a little finger that sticks out of a cell saying, "Come here big boy." It has another part that is underneath the cell wall that we'll talk about in a minute.

The surface of a cell is like a bunch of pine needles floating on a pond, only they float vertically instead of horizontally. They float in opposing pairs due to the fact that that long greasy tentacles like embracing other long greasy tentacles.
So Her2 receptors bob in the pond scum of the cell wall like a fishing float, waiting for something to happen. Waiting for a tickle from above.

When Her2Neu gets tickled, it does something interesting. The tickle is Epidermal Growth Factor or EGF. The interesting thing it does is this: If two Her2's are lined up, EGF causes a Mission Impossible fuse to light carrying a message to the nucleus of the cell, all the way to the core, and...


Something big happens. But first remember EGF arrives to dimerize.

You may know that before they launch the missile, two burly guys wear Club Nuke keys around their necks. They also wear pistols and agree to shoot each other if somebody tries to launch with one key. For a missile to be launched they have to agree. Then Vladamir and Alexeyev put the keys in the locks and turn them at the same time. Cause pretty much, all hell is fixin' to break loose. Music please.  
Trouble comes to town when somebody decides they're "special". They usually swagger in saying, "you don't need two keys" to fire the growth missile. "You only need one cuz I'm the boss of this little Tommy-Lee-Jones-little-piggy-Voodoo-Chile-of-a-movie. This cell under seige so to speak.

All because somebody couldn't wait. All because somebody had to get theirs first if you know what I mean.
In review:

When the EGF signal comes along, two Her2 receptors pair up. In
CellWorld™, the sets are struck and the whole theatre makes a copy of itself, right on the spot. This is a big operation and you don't want it "going off" without some checks and balances. I mean, you at least have to talk to an accountant. Making a new theatre, a new cell, or even a whole planet is a detailed, big budget affair.
Some people are born with bad boy genes and Tommy Lee is no different. When EGF shows up at the Her2Nu wedding reception, the party starts without the second keg even being bought, much less opened. Then only one key is needed to launch the missile. The result is a microscopic nuclear war called breast cancer. There are four reasons only one key is needed, and they all have to do with a little mistake, a little error that some call mutation. Mutations are real. They are happening right now to you and me. They have four causes which happen to be covered here.
You might want to stop here. After all, you were warned...
The Her2Neu Backstory


by Van Warren

For those who want to break the surly bonds of earth, and don their anti-gravity boots, there is an appendix to this story. It may clarify things for you. It may not. There is a little backstory on this Her2Neu thing. In a movie this story could be told with pictures instead of names. That would be better. I prefer a nomenclature free world, but life in a free world isn't always possible is it Neal? A picture can be a name, but I digress…

Light speed review:

Her2Neu is a receptor that forms pairs when a trigger is present. You can just see the trigger in the upper part of the picture. If you feel like you're translating hieroglyphics, you're not alone. Here's the pair at work on the right.



Epidermal Growth Factor is the Trigger

Now I told you everything above so I could just say this:


Her2Neu is part of the family of EGF Receptors and EGF Receptors belong to the family of tyrosine kinase receptors. This is important. Go get a coffee if you must, but promise yourself, like I did, that you will finish this no matter what happens.


Now we are going to decode tyrosine and kinase. It will take minute.


First Tyrosine.

Tyrosine is one of the twenty amino acids that we need to stay alive.

Our bodies make ten of these and Tyrosine can be synthesized by our cells so we don't need a Tyrosine supplement vitamin. This assumes a normal metabolism and a balanced diet. Some people have enzyme deficiencies, some have mental deficiencies including me, but that's my second feature film. Some choose to believe snake oil salesmen, instead of getting tested and supplemented correctly. But that is a war for another day. Speaking of war, I have to introduce you to Pvt. Tim Hall. Pvt. Tim Hall knows which aminos we must have. He knows because they are the letters of his name. We must dismember and eat Pvt. Tim Hall three times a day. This sounds worse than it is. Or not. It all depends on where you get your protein...

Expanding on the distinguished private's initials:


Phenylalanine Valine Tryptophan

                     Threonine Isoleucine Methionine

                                          Histidine Arginine Leucine Lysine

These are just the amino acids that our bodies, ourselves, can't make. So eat them already. Any ear of corn will do, and you don't have to run to the health food store.


One way to remember the amino acids is back when they toured as the "Singing Aminos". Here is a sketch of all twenty on stage at the Roxy. Ignore the notes, just look at the shape that makes each of them unique. Feel the charged atmosphere. It's charisma, not just looks. That's the take home message.

I know this picture is confusing, so I am promising myself to clean up, just like you promised yourself to finish this. Like most musicians, the Singing Aminos have three letter nicknames. If you know them really well you can call them by their one letter names. "Hey, Mr. Glycine, My Gly man, Life in the key of My Big G, Whassup on the G string? Anybody greased your palm lately boss? Right".


Before the Singing Aminos played in the jazz band, they made commercials.


Here they are holding hands, trying to teach the world to sing in perfect harmony:

Enjoy these little guys while you can, cuz this hallucination is coming to an end.


Before we leave, I want you to look at Serine and Tyrosine. They are special. Can you see what they share? If you said, "A little alcohol problem", you would be right! Threonine has an alcohol problem too, but he hides it and he gets away with it.


It turns out that the alcohol group, the "OH group", on them is a perfect parking place for a phosphate, aka Mr. P04. The perfect parking place for a little addiction.
A phosphorus atom is heavy man, and it holds 4 oxygens in the lotus position.

This phosphate group means underground action, cuz cells NEED phosphate BAD.

Phosphate is where the energy for doing stuff comes from, and also the growth signal when it comes time to put more bleachers in the new gym.


Forget Rachel Carson, forget Silent Spring, without phosphate in the right place, spring is silent. But a phosphate in the wrong place at the wrong time, well that is nuclear winter, complete with fallout of the hair.

Quick review.

All proteins are just strings of amino acids.

There are two kinds of proteins:

 - enzymes: the little micromachines that make stuff happen,
 - structural proteins that make hair, skin, connective tissue, collagen, etc.
Collagen is a triple helix consisting of lots of kinky pralines (not pralines) to give it strength.

People are big gobs of protein that, like cells, want to make copies of themselves.

One of those proteins is Tyrosine.

Tyrosine holds phosphate.

So that covers Tyrosine.


This is almost over if you can believe it. We will finish with the kinase.

A kinase is an enzyme (machine) that parks a phosphate on an OH group, thus the alcohol problem. So we're done. Remember only this:


When two Her2Nu receptors get together in the presence of EGF, they phosporylate each other, since they are tyrosine kinases. This triggers a growth fuse that we can talk about some other time. EGF is a modular signal that plays a large number of roles depending on the assembly of the signal. To see other uses of EGF click here. This game is over. You finished.