aka cell-cell signaling. See also Intracellular signaling

Main stages of cell-cell signaling

1. Signal generation
2. Transportation
3. Reception
4. Transduction
5. Cellular reponse

Signal transportation

Forms of cell-cell signal transportation in vertebrates

https://www.wikiwand.com/en/Cell_signaling#/Classification

• Juxtacrine. contact deoendent.
• DIrect signalling – gap junction. In Plant cells, plasmodesmata. The fastest. milliseconds. Diffusion + potential.
• Intracrine. Stay within the cell.
• Autocrine
  • Reinforces the signal
  • Community (cooperative effect)
• Paracrine. Affects local environment.
  • Examples: wound healing, response to allergens.
• Synaptic. Long-range and fast. Neurons in Neuronal networks.
• Endocrine. Long range and slow. Hormones. Travels through the Blood vessels

Signal reception

• Receptor on the plasma membrane
• Intracellular response, but then signal needs to be Hydrophobic to travel Cell membrane

Cell-surface receptors

• Ion channel coupled receptors
• G-protein coupled receptor
• Enzyme coupled receptor

Intracellular receptors

• Steroid hormone receptors
• Estrogen receptors

Signal transduction

Intracellular (within a Cell) processes networks (of protein interactions) to respond and generate signals for Cell signaling

Experimental investigation of cell signaling

Main challenge: label the proteins with the cell from which they originate, so that, from the Proteomics analysis, we can know where each protein comes from in a multi-cellular culture (coculture), and study their individual responses to their mutual cell-cell signaling.

• stable isotope labelling with Amino acids in Cell culture (SILAC), good for short term effects of cell-cell communication (Jorgensen et al., 2009).
• a cross-​ species proteomics approach which involved comparing the prote- omes and phosphoproteomes of cancer cells grown in isolation in vitro with those of the same cells grown in mouse xenografts. Rajeeve et al.
• cell type-​specific labelling using amino acid precursors (CTAP), exploits the well-​known inability of animal cells to synthesize essential amino acids, such as lysine. Transgenic ex- pression of amino acid synthesizing enzymes (from fungi or plants) in human or mouse cells allows these to incorporate labelled amino acid precursors into proteins. Expression of distinct amino acid synthesizing enzymes in different cell lines permits these to stably express labelled proteins with amino acids differing in mass, thus enabling the determination of relative abundance of proteins from different cell types growing in coculture (Gauthier et al., 2013). a limitation of CTAP is that, as cells need to be cultured with labelled amino acid precursor, it cannot easily be applied in in vivo studies. is the idea that one can substitute certain aminoacids in proteins with similar ones but with different mass, thus labeling the protein without significantly affecting its function?
• Blocking Specific Kinases With Inhibitors
• Cell Behavior Assays
• Visualizing Signal Transduction Events
• Western blots
• Immunoprecipitation
• GST Binding or “Pull-Down” Assays
• Activity Assays
• Using a Combination of Western blots, Immunoprecipitation, and GST Pull-Down Assays

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2862383/ (2002. I'm sure there are many new techinques by now)