signalling across membranes

Peter Dudek peterd at primeachip.com
Wed Jun 27 12:11:16 EST 2001


For GPCR signaling, see the following (there are many many excellent reviews
on the subject, but this will give you a good start):

1. Shea and Lindermann. 1997. Mechanistic model of G-protein signal
transduction.... Biochem. Pharmacol. 53:519-530.
2. Schoneberg et al. 1999. Structural basis of G protein coupled receptor
function. Mol. Cell. Endocrinol. 25:181-193.
3. Morris and Malbon. 1999. Physiological regulation of G protein-linked
signaling. Physiol. Rev. 79:1373-430.
4. Liebmann and Bohmer. 2000. Signal transduction pathways of G
protein-coupled receptors and the cross-talk with receptor tyrosine
kinases... Curr. Med. Chem. 7:911-943.

As for your RTK question, I don't have any reviews I can share immediately,
however, to answer your question, as far as I know, the insulin growth
factor receptors (like many RTKs, PDGF, EGF etc) are activated when
dimerized by their respective growth factors (which you might want to
imagine as being a multivalent molecule, that binds to multiple receptors at
the same time on the cell surface). The receptors are activated because
their intracellular kinase domains are brought into close proximity to
regions on adjacent receptors that contain tyrosine motifs, which get
phosphorylated. These tyrosines make particularly good binding sites for
SH2-domain containing signaling molecules (like the tyrosine kinase Src, for
instance).

In any case, to make a long and complicated story short, you can think of
the signaling to occur like the following: growth factor binds receptor ->
receptor dimerizes -> intracellular domains phosphorylate each other ->
phosphorylated domains bind and activate other signaling molecules ->
signaling molecules elicit further responses.

There are countless great reviews on the subject, and they should be rather
easy to find, just do a PubMed search (like "receptor AND tyrosine AND
kinase AND signaling AND review", or something similar). Alternatively, you
can go to Science's Signal Transduction website here:
http://stke.sciencemag.org/index.dtl.

Happy reading,

Peter D

> Dear Netters,
>
> I'm not an expert in animal signal transduction and find it quite tought
> to resolve the following questions. If you know a good review covering
> the aspects or have your personalized answer, I would be very happy to
> receive an answer!
>
> How do the 7 transmembrane (G-protein coupled) receptors signal the
> information across the membrane? is there anything known which is more
> specific than the rather fuzzy "conformational change"...?
>
> what about the Insulin receptor? usually for the receptor tyrosine
> kinases it's said that the dimerization is the trigger - but insulin
> receptor is allready dimerized... - so what's the trigger?
>
> Thanx very much for your kind help!
> Jens
>
> lohrmann at sun2.ruf.uni-freiburg.de
>
> ____________________________________________________________
> Jens Lohrmann
>
> lohrmann at sun2.ruf.uni-freiburg.de
>
> http://www.biologie.uni-freiburg.de/data/schaefer/jl01.html
> http://www.biologie.uni-freiburg.de/data/schaefer/jl02.html
> ____________________________________________________________
> dienstlich:
>
> Schänzlestr. 1
> Institut für Biologie II / Botanik
> 79104 Freiburg
> Fon: 0761/203-2619
> Fax: 0761/203-2612
> ____________________________________________________________
> privat:
>
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>





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