ERK 2 Substrates

CD45 (Ser 940) plays a pivotal role in immune cell signaling, particularly through its phosphatase activity. Phosphorylation at this serine residue by ERK 2 modulates CD45's conformation, impacting its interaction with various substrates. This modification fine-tunes the activation threshold of T-cell receptors, influencing downstream signaling pathways. The kinetics of this phosphorylation event are crucial for regulating immune responses, thereby affecting cellular activation and differentiation processes.

Cdc6 (Ser 54) is integral to the regulation of DNA replication, particularly through its interaction with the pre-replicative complex. Phosphorylation at this serine residue by ERK 2 alters Cdc6's conformation, enhancing its affinity for other replication factors. This modification is essential for the timely assembly of replication origins, influencing the kinetics of DNA synthesis. The precise timing of this phosphorylation event is critical for maintaining genomic stability during the cell cycle.

Cdc6 (Ser 106) plays a pivotal role in the initiation of DNA replication, particularly through its dynamic interactions with various cell cycle regulators. Phosphorylation at this serine residue by ERK 2 induces conformational changes that modulate Cdc6's binding affinity to the origin recognition complex. This modification is crucial for the recruitment of additional factors necessary for replication fork formation, thereby influencing the overall efficiency and timing of DNA replication processes.

Cdc25C (Ser 216) is a critical phosphatase that regulates the cell cycle by activating cyclin-dependent kinases (CDKs). Phosphorylation at Ser 216 by ERK 2 enhances its enzymatic activity, promoting the dephosphorylation of CDK substrates. This action accelerates the transition from G2 to M phase, facilitating mitotic entry. The precise regulation of Cdc25C through this phosphorylation event is essential for maintaining proper cell cycle progression and ensuring genomic stability.

Connexin 43 (mSer 262) is a pivotal gap junction protein that plays a crucial role in intercellular communication. Phosphorylation at Ser 262 by ERK 2 modulates its channel activity, influencing the permeability and conductance of gap junctions. This modification alters the dynamics of cellular signaling pathways, impacting processes such as cell growth and differentiation. The interaction of connexin 43 with other proteins further enhances its regulatory functions in tissue homeostasis.

Elk-1 (Ser 383) is a transcription factor that integrates signals from the ERK 2 pathway, influencing gene expression through specific phosphorylation. The modification at Ser 383 enhances its binding affinity to DNA, facilitating the recruitment of co-activators and chromatin remodeling complexes. This dynamic interaction modulates transcriptional responses to growth factors, thereby impacting cellular processes like proliferation and differentiation. Elk-1's role in signal transduction highlights its importance in cellular adaptation.

ERα (Ser 104/106) is a key player in the signaling cascade involving ERK 2, where its phosphorylation at these serine residues alters its conformation and enhances its interaction with co-regulatory proteins. This modification promotes the recruitment of chromatin remodeling factors, thereby influencing transcriptional activity. The distinct kinetics of ERα's phosphorylation and its subsequent effects on gene regulation underscore its role in mediating cellular responses to hormonal stimuli.

FADD (Ser 194) serves as a crucial adaptor protein in the ERK 2 signaling pathway, where its phosphorylation at this specific serine residue modulates its binding affinity to downstream effectors. This modification facilitates the assembly of signaling complexes, enhancing the propagation of apoptotic signals. The unique interaction dynamics of FADD with other proteins in the pathway underscore its role in fine-tuning cellular responses to stress and growth signals, impacting cell fate decisions.

FAK (Ser 722) is a pivotal player in the ERK 2 signaling cascade, where its phosphorylation at this serine residue influences its interaction with various scaffolding proteins. This modification alters the kinetics of signal transduction, promoting the formation of multi-protein complexes that amplify cellular responses. The distinct conformational changes induced by FAK's phosphorylation enhance its role in mediating cellular adhesion and migration, thereby impacting cytoskeletal dynamics and cellular architecture.

IPP-1 (Ser 67) serves as a critical modulator within the ERK 2 pathway, where its specific phosphorylation enhances binding affinity to downstream effectors. This modification facilitates unique allosteric changes, promoting the assembly of signaling complexes that drive cellular proliferation and differentiation. The kinetic profile of IPP-1's interactions reveals a rapid turnover, allowing for precise temporal regulation of signal propagation, ultimately influencing cellular fate decisions.