Hypothesized pathways in pathogenesis of cardiovascular disease (WP3668)

The pathways hypothesized to be involved in cardiovascular diseases begin with LTBPs and fibrillins activating a TGFBR complex. The complex can begin the canonical TGFB pathway involving SMAD proteins that target gene expression for proteins involved in endocardial and epicardial EMT, neural crest migration, ECM remodeling, cell differentiation, development and maintenance of cardiovascular structure and function. The non-canonical TGFB pathway involves the calcium-calneurin signaling pathway that also affects those functions. The TGFBR complex also activates SHCA and Tak1, which promote the function of a complex (ERK1/2, JNK1, and p38) to regulate the previously mentioned cell functions and influence the development of cardiovascular diseases. These diseases are additionally influenced by a signaling pathway involving the activation of TGFB ligands, receptors, activators, and effectors by ANG2/AT1/2R complex. This pathway is based on figure 1 from Doetschman et al. Proteins on this pathway have targeted assays available via the [https://assays.cancer.gov/available_assays?wp_id=WP3668 CPTAC Assay Portal]

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