Receptor crosstalk: Communication through cell signaling pathways

Abstract

The response of cells to extracellular stimuli is mediated in part by a number of intracellular signal transduction pathways. The frequent lack of a one-to-one correlation between receptor activation and intracellular responses, such as predictable nuclear transcription events, is perplexing. This lack of correlation, however, suggests that various signaling pathways intersect and crosstalk to modify and influence the biological outcome of a specific extracellular signal. In this review, the basic pathways and aspects of signal transduction are laid out, and known sites of crosstalk are discussed. A clearer understanding of receptor and cell signaling pathways and levels of crosstalk should provide insight into the paradoxes that underlie both imprecision and predictability in signal transduction.

Crosstalk and the evolution of specificity in two-component signaling

“…Signaling networks in eukaryotes display extensive "crosstalk," with individual kinases acting on large numbers of targets: the kinase Cdk1, for instance, has hundreds of substrates in yeast (9)(10)(11). Bacterial TCS networks show a remarkably different topology: HKs usually act on a single target (12)(13)(14)(15)(16)(17).…”

Olfactory coding in Drosophila larvae investigated by cross-adaptation

“…This fact is telling us something about the mechanisms involved in mediating the olfactory response after pre-stimulation. Both this decline in attractiveness and the overall phenomenon of cross-adaptation could be an example of receptor cross-talk, where stimulation of one class of receptor leads to an alteration (generally a potentiation) of the response of another receptor class (Hill, 1998). Cross-talk often involves protein phosphorylation mediated by G-protein coupled receptor kinases within a given neuron (Vasquez-Prado et al, 2003), such as those implicated in olfactory adaptation in C. elegans (L'Etoile et al, 2002).…”

Atypical expression of ErbB3 in myeloma cells: cross-talk between ErbB3 and the interferon-α signaling complex

“…A variety of biologic and molecular factors, including altered tumor cell growth factor responsiveness and receptor expression, likely account for this heterogeneity and the accompanying challenge in treating this disease. An added biological challenge is introduced by the ability of some receptors to act in a nonlinear fashion and transactivate unrelated receptors, thereby perhaps providing an attractive mechanism by which tumor cell growth factor/cytokine responses can be amplified (reviewed by Hill, 1998). Given that tumor cells, including myeloma cells, often acquire atypical expression of one or more signaling receptors during malignant transformation (reviewed in Bregman and Sipes, 1986), from a therapeutic standpoint, it becomes imperative to understand fully the nonlinear signaling in myeloma cells.…”