Molecular Signaling Overview

Principles

Definition

Molecular signaling is the academic field that investigates how cells perceive and respond to cues from their environment and other cells. It studies the complex networks of molecular interactions and pathways that transmit information internally and externally, enabling the coordination of diverse biological processes essential for development, homeostasis, and adaptation.

Ontological type

Core Pathways

Signal Transduction Mechanisms

Pathological Dysregulation

Key developments

Key Figures

Network Integration Era era

Matthias Mann[1], associated with Harvard University[3] and the Massachusetts Institute of Technology[4], was a leading figure in the Network Integration Era. His contributions in this era include applying proteomic mapping of signaling complexes and, as reflected in the FLICE paper[6], revealing how a FADD-homologous ICE/CED-3–like protease is recruited to the CD95 (Fas/APO-1) death-inducing signaling complex, thereby clarifying how caspase activation integrates into death-receptor networks and enabling network-level interpretations of apoptosis. Peter H. Krammer[2], linked to Harvard University[3] and the Weizmann Institute of Science[5], contributed to decoding death-receptor signaling pathways during this era. As a co-author of the FLICE paper[6], he helped define the recruitment and activation of caspases at the DISC, reinforcing the network-centric view of signaling and informing therapeutic targeting approaches in this era.

Cyclic Dinucleotide Immunity era

Zhijian J. Chen [1] is associated with The University of Texas Southwestern Medical Center [2] and the University of Pennsylvania [3] during the Cyclic Dinucleotide Immunity era. His key contribution was identifying cyclic GMP-AMP (cGAMP) as an endogenous second messenger in innate immune signaling by cytosolic DNA, as demonstrated in the 2012 paper Cyclic GMP-AMP Is an Endogenous Second Messenger in Innate Immune Signaling by Cytosolic DNA [4]. This discovery linked cytosolic DNA sensing to STING-mediated signaling [4], establishing a second-messenger paradigm that underpins innate immunity and cancer immunotherapy in this era. Together, Chen's work on cGAMP has shaped therapeutic strategies by highlighting cGAMP [4] as an endogenous messenger and guiding future exploration of nucleic-acid sensing in vaccines and immunotherapies.

Receptor-Scaffolded Inflammation era

Masayuki Yamamoto [1] is a prominent figure in the Receptor-Scaffolded Inflammation era, with affiliations spanning the National Institute for Basic Biology [2] and the University of Pittsburgh [3]. The 2016 paper 'Nrf2 suppresses macrophage inflammatory response by blocking proinflammatory cytokine transcription' [4] demonstrates that redox-regulated transcriptional control can dampen inflammatory signaling, illustrating how scaffolded architectures and biased signaling interface with transcriptional programs in this era. Yamamoto [1]’s work thus embodies the era's shift toward understanding how biophysical modulators and scaffold geometry shape inflammatory outcomes. This perspective underscores the centrality of integrating redox state with transcriptional gating to control macrophage responses, a theme that sits at the core of Yamamoto [1]’s contributions in this era.