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I heard somewhere that activating any receptor results in the same intracellular response (signaling) which involves NF-κB. If that is true, I hardly understand how the cells distinguish between different types of stimulis coming from different types of receptors. I guess I am missing the point... :S

signal transduction

  • Figure 1 - signal transduction - source

If you check this picture about signal transduction. What you can see that there are about 10 arrows pointing to the inside of the nucleus, and there are about 10 receptor categories involved. Afaik. there are much more genes in the nucleus, so how is it possible to regulate the expression of so many genes with only a few signaling pathways?

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    $\begingroup$ I don't have an answer other than to say that signal transduction is an immensely complex interaction of many different proteins. The schematic you posted represents idealized pathways and omits a lot. Also, how a cell responds to a signal (ie which genes become activated) is largely dependent on the state the cell is already in. $\endgroup$ – canadianer Nov 11 '14 at 4:28
  • $\begingroup$ Short answer: No, it's not like this. First, there is a broad variety of different receptors and then there is a wide variety of different receptors within one class. GPCR are not all the same for example, their G$\alpha$-parts are not the same. The same is true for RTKs, which are grouped on homology, but have different ligands for example. I can write a more comprehensive answer later, as this is a complicated topic. $\endgroup$ – Chris Nov 11 '14 at 6:53
  • $\begingroup$ In concur with @Chris: no $\endgroup$ – AliceD Dec 11 '14 at 12:14
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It's a complicated answer. More than 200 cell types, each type of cell inherits a unique expression of receptors, internal and external. Diffusion of signals through the plasma membrane and/or nuclear compartment may act directly as cofactors, activators, etc. The specific sequestration, and pattern of expression of external receptors also influence what signals become bound and relayed. The cell will also have a motif of internal/cytoplasmic/nuclear proteins expressed that complex or become directly activated by interaction with any of the above, etc. So the currently expressed set of internal, and external proteins determine not only how the cell interprets the signal, but also how they respond.

As for the actual genetic material, you'll find inherited motifs like DNA methylation, histone acetylation patterns etc. influence what parts of the DNA can actually be accessed. Per the above schema of signaling pathways, the signals received by each individual cell differ based on the actual cell type. In any case there are patterns of activators/repressors, enhancers/silencers that are switched on or off by these signals. Some journals are also introducing evidence insoluble receptors like EGFR+ligand can actually internalize and translocate to the nucleus and act as transcription regulators.

The final note, is that due to alternative splicing and transcription of proteins that promote or repress splicing sites, in a combination with the above concepts a cell can regulate for thousands of genes. This is a very general answer, however. The concept to take home, though, is that differentiated cells have their own specific motifs they express that make "reading" different signals possible, and also makes differing responses to what could be the same signal possible. These motifs also allow for the accurate expression of the relevant portions of the genome (not all genes are expressed at all times in all cells).

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I heard somewhere that activating any receptor results in the same intracellular response (signaling) which involves NF-κB.

I don't think all receptors activate NF-κB (Pro-growth signals activate it, mostly).

how the cells distinguish between different types of stimulis coming from different types of receptors.

The cell need not, sometimes, know where and how the signal came from, unless it has to interact back to the origin of signal (as in case of neural synapses). Some pathways such as growth and inflammation can be triggered by many kinds of signals; the responses generally converge to a common pathway (If all that cell has to do is to boost up inflammation, then it would be costly for the cell to keep a unique pathway for each kind of trigger.)

there are much more genes in the nucleus, so how is it possible to regulate the expression of so many genes with only a few signaling pathways?

Some genes are co-regulated because they fall in the same pathway. They collectively comprise what is known as a regulon.

Also, it is possible that multiple signaling pathways have a different response in combination compared either of them individually. Such mechanisms exist in differentiation pathways during development (Can't think of an exact example; will provide one in a while).

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