A Thousand and One Receptor Tyrosine Kinases: Wherein the Specificity?

Over 20 years ago, a series of seminal studies in PC12 neurons provided a framework for how receptor tyrosine kinases generate many different outcomes despite activating a set of shared intracellular pathways. In this essay, we revisit the question of receptor tyrosine kinase specificity. We first examine the relationship between receptor phosphorylation and intracellular pathway activation. We then consider the mechanisms through which signaling dynamics encode distinct cellular outcomes and finally discuss how two different receptors drive divergent transcriptional responses within the same developmental context. Establishing the key parameters that dictate the response to growth factor stimulation is critical for determining how receptor tyrosine kinases orchestrate development, an essential prerequisite for understanding the pathological consequences when such signaling processes go awry.