Now that one story is on pause, let's turn to another story and another set of blog entries. I'll begin with something I previously posted a few months ago.

Let'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"¦.

This entry was posted on Wednesday, June 18th, 2008 at 9:48 pm and is filed under Repost. You can follow any responses to this entry through the RSS 2.0 feed. You can leave a response, or trackback from your own site. The trackback link is: http://telicthoughts.com/receptor-tyrosine-kinases-2/trackback/