High affinity cGMP-specific 3';5'-cyclic phosphodiesterase 9A; also known as PDE9A; is a member of the cyclic nucleotide phosphodiesterase family and PDE9 subfamily. PDE9A is expressed in all tissues examined (testis; brain; small intestine; skeletal muscle; heart; lung; thymus; spleen; placenta; kidney; liver; pancreas; ovary and prostate) except blood. Highest levels of PDE9A is in brain; heart; kidney; spleen; prostate and colon. IsoformPDE9A12is found in prostate. PDE9A mRNA is widely distributed throughout the rat and mouse brain; with the highest expression observed in cerebellar Purkinje cells.PDE9A is the only cGMP-specific PDE with significant expression in the forebrain; and as such is likely to play an important role in NO-cGMP signaling. PDE9A is highly conserved between species and is widely distributed throughout the rodent brain. PDE9A is probably involved in maintenance of low cGMP levels in cells and might play an important role in a variety of brain functions involving cGMP-mediated signal transduction. PDE9A hydrolyzes the second messenger cGMP; which is a key regulator of many important physiological processes. PDE9A represents a novel drug target worthy of further study.
Platelet-derived growth factor subunit A (PDGFA); belongs to the PDGF/VEGF growth factor family. PDGFA is a secreted protein; stored in platelet alpha-granules and released by platelets upon wounding. PDGFA is potent mitogens for a variety of cell types including smooth muscle cells; connective tissue cells; bone and cartilage cells; and some blood cells. It plays an essential role in the regulation of embryonic development; cell proliferation; cell migration; survival and chemotaxis. PDGFA is required for normal lung alveolar septum formation during embryogenesis; normal development of the gastrointestinal tract; normal development of Leydig cells and spermatogenesis; normal oligodendrocyte development and normal myelination in the spinal cord and cerebellum. It plays an important role in wound healing; Signaling is modulated by the formation of heterodimers with PDGFB.
Platelet-Derived Growth Factor Subunit B (PDGFB) belongs to the PDGF/VEGF growth factor family. Platelet-derived growth factor is a potent mitogen for cells of mesenchymal origin. PDGFB can exist either as a homodimer (PDGF-BB) or as a heterodimer with the platelet-derived growth factor alpha polypeptide (PDGF-AB), where the dimers are connected by disulfide bonds. Mutations in this gene are associated with meningioma.Binding of PDGFB to its receptor elicits a variety of cellular responses. In addition, PDGFB is released by platelets upon wounding and plays an important role in stimulating adjacent cells to grow and thereby heals the wound.
PDGFRA; also known as CD140a; together with the structurally homolog protein PDGFRB (CD140b); are cell surface receptors for members of the platelet-derived growth factor family. They are members of the class III subfamily of receptor tyrosine kinase (RTKs) with the similar structure characteristics of five immunoglobulin-like domains in their extracellular region and a split kinase domain in their intracellular region. PDGFRA is expressed in oligodendrocyte progenitor cells and mesothelial cell; and binds all three ligand isoforms PDGF-AA; PDGF-BB and PDGF-AB with high affinity; whereas PDGFRB dose not bind PDGF-AA. PDGFRA plays an essential role in regulating proliferation; chemotaxis and migration of mesangial cells. Recent studies have indicated that PDGFRA acts as a critical mediator of signaling in testis organogenesis and Leydig cell differentiation; and in addition; particularly important for kidney development. Additionally; PDGFRA is involved in tumor angiogenesis and maintenance of the tumor microenvironment and has been implicated in development and metastasis of Hepatocellular carcinoma (HCC). PDGFRA may represent a potential therapeutic target in thymic tumours. PDGFRA gene amplification rather than gene mutation may be the underlying genetic mechanism driving PDGFRA overexpression in a portion of gliomas.
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