Signal transduction enables cells to sense and respond to chemical and mechanical information in the extracellular environment. Recently, phase separation has emerged as a physical mechanism that can influence the spatial organization of signaling molecules and regulate downstream signaling. Although many molecular components of signaling pathways, including receptors, kinases, and transcription factors, have been observed to undergo phase separation, understanding the functional consequences of their phase separation in signal transduction remains an ongoing area of research. In this review, we will discuss recent studies investigating how cells potentially use phase separation to regulate different signaling pathways by initiating signaling, amplifying signaling, or inhibiting signaling. We will also discuss recent observations that suggest a role for phase separation in mechanosensing in the Hippo pathway and at focal adhesions.
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