I am in an embryology course right now and we've just started covering cell-cell communication in development. We were talking about the roles of the various cadherins and their discoveries but we got to cell signaling pathways and in reading my textbook I'm finding myself confused by these pathways-- some of those that are mentioned include Notch, Wnt, FGF, TGF-beta, RTK, Jak-Stat, SMAD, integrins, PTHrP, Hedgehog, Discoidin domain receptors 1&2, and the unfolded protein response (UPR).

I know the RTK pathway and I know the SMAD pathway, but the others just seem to be specific ligands that are using these pathways -- is this correct?

  • $\begingroup$ In contrast to each and every one that I listed having its own distinct pathway. $\endgroup$ – Alexandria Mar 1 '13 at 4:42
  • $\begingroup$ Not sure what you mean. Notch has its own pathway, as does wnt and tgf-beta. Don't remember the other off the top of my head. Why don't you check them out on kegg? $\endgroup$ – terdon Mar 1 '13 at 11:05
  • $\begingroup$ see my comment on the post below -- I could have done a much better job saying what I was confused about in writing this question. $\endgroup$ – Alexandria Mar 1 '13 at 15:04

@Alexandria Jak/Stat are two families of proteins which mediate signals through phosphotyrosines.

JAK is a tyrosine kinase which binds to cell receptors and STAT is dimerized by JAK action. JAK specificity seems to be your question. A specific JAK protein (e.g. JAK1 or JAK2..) may mediate for different receptors in different cells.

There may be hetero- or homo-dimers of JAK, there may be more than one receptor in a cell using the same JAK enzyme, which may result in cross-talk between the two signals. I think its a pathway dynamic that can vary quite a bit from one cell to another, depending on the receptor and cytokine environment the cell is seeing. JAK action can be modulated by any number of proteins which respond to other pathway signals or the cell state. The diagram below from a review of heart muscle cell JAK action is not unusual nor is it complete.

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With the exception of Jak/Stat, all of the proteins you mentioned are ligands and/or receptors. When a ligand binds to a receptor, it induces one or more cell signaling pathways, which are dependent on intracellular proteins being activated via association with the receptor, then going on to activate other proteins in a signaling cascade that eventually results in the cell doing something - usually involving regulating gene transcription to make proteins that effect the change - such as altering the cell's developmental fate to become more specialized, for example.

Jak/Stat is an example of a cell signaling pathway, that is also fairly straightforward to understand. Various members of the Jak family are loosely associated with a variety of receptor proteins. When those receptors are activated by a ligand binding to them, Jak becomes activated and recruits various members of the Stat family of transcription factors. The Stats become activated and dimerize (form doublets), then translocate to the nucleus and bind specific promoter regions of DNA. They then recruit the rest of the DNA transcription machinery to transcribe these target genes. The gene products then help effect the cell's response to the original stimulation - the binding of the ligand to the receptor.

  • $\begingroup$ Thank you, but I do understand that -- I suppose I didn't write my question very well and I was initially confused because my book explains the receptor tyrosine kinase (RTK) pathway in the context of the fibroblast growth factor family of paracrine factors, because the FGF receptors are RTK's. I was wondering how much of this "sharing" takes place -- how many of these ligands use the RTK pathway? My book implies that quite a few do, but isn't explicit about which. $\endgroup$ – Alexandria Mar 1 '13 at 15:03

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