Chunk #31 — RESULTS — Differential expression of signaling proteins in calcium, cyclic nucleotide and small GTPase 2nd messenger pathways in PCPs — Ras and Rho small GTPases
Many cell surface receptors signal through a large set of Ras superfamily small GTPases to activate multiple kinase cascades that engage effectors, including transcription factors that regulate gene expression and cytoskeleton proteins that regulate cell shape, motility, adhesion and intracellular transport (Alberts et al., 2014). The mammalian genome contains ~30 Ras-GTPases and ~ 20 Rho-GTPases, each is regulated by several dozens of guanine nucleotide exchange factors (GEFs) and inactivated by GTPase activating proteins (GAPs) (Cherfils and Zeghouf, 2013). Within the Ras family, 21 of the 32 members showed major enrichment in specific PCPs (AUROC=0.84). As different Ras family members might be activated by different upstream signals, have different cellular functions, and engage different downstream effectors (Alberts et al., 2014), PCPs might use Ras members to relay distinct external inputs and trigger appropriate transcription programs and other effectors that mediate long term cellular changes. Furthermore, both the Rho-GTPases and Rho-GEFs are differentially expressed. 37 of the 57 Rho-GEFs (AUROC=0.82) and 14 of the 19 Rho-GTPases (AUROC=0.72) are enriched in specific PCPs (Figure 5D, S5C-D). As different Rho members are often activated
