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Pathway Network Analyses for Autism Reveal Multisystem Involvement, Major Overlaps with Other Diseases and Convergence upon MAPK and Calcium Signaling

Fig 3

Integrated MAPK and calcium signaling in ASDs.

a. Overlapping genes in calcium and MAPK signaling pathways. b. The voltage-gated calcium channel mediates the influx of Ca2+, which modulates PKC and Ras. Growth factors bind to the extracellular domain of receptor tyrosine kinases (RTKs), and signal molecules Grb2 (growth factor receptor-bound protein 2) and Sos (son of sevenless) are consequently recruited to the internal docking site, resulting in Ras activation. Ras triggers a phosphorylation cascade including Raf and MEK. This leads to ERK activation and translocation to the nucleus, where ERK then activates transcription factors that mediate gene expression. The ASD genes are listed in light blue frames close to the corresponding gene products that are shown in orange.

Fig 3

doi: https://doi.org/10.1371/journal.pone.0153329.g003