1
$\begingroup$

Receptor Tyrosine Kinases (RTKs) present themselves on the surface of a cell as monomers until a ligand (such as a mitogen) binds and causes the formation of the active dimer. However I do not understand why truncations are so commonly seen in retrovirally delivered oncogenes or in oncogenic mutations. My confusion here is that if mitogen binding of RTKs facilitates the close proximity of two monomers, then simple overexpression should allow for increased transphosphorylation of monomers, and therefore be mitogenic (which it does). But then what advantage would a truncation that removes the extracellular portion of an RTK have in increasing transphosphorylation of monomer units?

$\endgroup$
  • $\begingroup$ I've edited this a little (defined the abbreviation as a start) but the question is so badly expressed I think it should be let die in the absence of a revision of the answer provided by @Mr-Bauer providing references. $\endgroup$ – David Feb 2 '17 at 13:33
1
$\begingroup$

As you said the simple overexpression can lead to transphosphorylation and activation of mitogenic signalling. This helps the cancerous cells to survive.

By truncation of the molecule the cell also gains a benefit, because it could prevent inhibition of the receptor from outside the cell. The truncation furthermore could be induced by treating cancer with inhibitory antibodies against the receptor. For example a treatment with anti-EGFR antibodies could induce resistance by mutation and selection. One of this mutations could be the truncation of the receptor.

$\endgroup$
  • 1
    $\begingroup$ Welcome to Bio. References are appreciated here, most notably when making strong statements like anti-EGFR antibodies like Cetuximab could induce an evolution of the cancer cells whereby the truncation of the receptor benefits the cancerous cells. $\endgroup$ – AliceD Dec 8 '15 at 20:34
  • $\begingroup$ nature.com/nrclinonc/journal/v7/n9/full/nrclinonc.2010.97.html maybe $\endgroup$ – CKM Dec 8 '15 at 20:53
  • $\begingroup$ Though I have to agree, it basically says "Hey, nothing wrong, nothing to regulate here" to the outside of the cell, much like truncated NKG2D ligands make it harder for immunosurveillance to do it's job. $\endgroup$ – CKM Dec 8 '15 at 20:58
  • $\begingroup$ Thanks for the comment, I changed my answere a little bit. $\endgroup$ – Mr-Bauer Dec 9 '15 at 16:00
  • $\begingroup$ The reference from Kendall is very good. Also I would reference this paper link to show annother treatment induced mutation of cancer. $\endgroup$ – Mr-Bauer Dec 9 '15 at 16:04

Your Answer

By clicking “Post Your Answer”, you agree to our terms of service, privacy policy and cookie policy

Not the answer you're looking for? Browse other questions tagged or ask your own question.