Disease relevance of Dab2

• Activation of the terminal complement cascade involving C5 to C9 proteins has a beneficial role for oligodendrocytes (OLG) in experimental allergic encephalomyelitis, an animal model of multiple sclerosis, by protecting them from apoptotic cell death [1].
• Therefore, we tested the hypothesis that in neonatal rats subjected to a unilateral HI cerebral insult, prior administration of E. coli lipopolysaccharide (LPS) augments (1) complement-mediated serum hemolytic activity, and (2) C3 mRNA and C9 mRNA levels in hepatic and cerebral tissue [2].
• Defibrase DF-521 batroxobin down-regulate ICAM-1 and complement C3d and C9 expression in the perihematomal area, and attenuate brain edema formation in ICH rats [3].
• Immuno-histochemistry also showed that C3d deposition reduced significantly, and the Western blot analysis also showed the content of C9 protein declined around the hematoma in DF-521 batroxobin treatment group at 72 hours after ICH [3].

High impact information on Dab2

• Northern and Western blot analyses indicated that Doc2 is present in PC12 cells [4].
• We previously isolated a new protein having two C2-like domains which interacted with Ca2+ and phospholipid and named Doc2 (Double C2) [4].
• Doc2 enhances Ca2+-dependent exocytosis from PC12 cells [4].
• In the PC12 cells transfected with a plasmid with the coding sequence of Doc2 in the antisense orientation, the high K+-induced release of co-expressed GH was inversely inhibited [4].
• Because Doc2 was abundantly expressed in brain where it was highly concentrated on the synaptic vesicle fraction, we have examined here whether Doc2 is involved in Ca2+-dependent exocytosis from cultured PC12 cells [4].

Biological context of Dab2

• To unveil the function of C9 in cell growth, we transfected p59 complementary DNA into the C4-2 cells, a derivative of the LNCaP prostatic carcinoma cell line [5].
• Dab2 is a mitogen-responsive phosphoprotein thought to be an adaptor molecule involved in signal transduction, and a suggested negative regulator of cell growth [6].
• The double C2 domain protein family (DOC2) is characterized by two calcium-binding domains (C2) [7].

Anatomical context of Dab2

• Taken together, our results suggest that C9 is up-regulated during prostate degeneration process and may play an active role in the proliferation and differentiation of prostatic epithelium [5].
• Immunohistochemical analysis of rat VP demonstrated that C9 is detected in the basal epithelia and surrounding stromal cells after prolonged castration [5].
• Doc2 is not associated with known regulated exocytotic or endosomal compartments in adrenal chromaffin cells [8].
• We conclude that Doc2 is not a general component of regulated secretory vesicles, but may instead be associated with mitochondria [8].
• To examine whether Doc2 is associated with synaptic-like microvesicles (SLMVs) or dense-core granules in neuroendocrine cells, we examined the distribution of Doc2 in subcellular fractionation of chromaffin cells of the adrenal medulla and in PC12 cells [8].

Associations of Dab2 with chemical compounds

• The Doc2 mutant expressing an N-terminal fragment or a C-terminal fragment containing two C2-like domains inhibited the high K+-induced release of co-expressed GH [4].
• Hepatic and cerebral C3 mRNA and C9 mRNA were quantified by qRT-PCR at 3, 6, and 18 h after HI [2].
• Cerebral C9 mRNA was not detected and was not affected by HI, with or without the prior LPS administration [2].

Analytical, diagnostic and therapeutic context of Dab2

• RT-PCR revealed the expression of ubiquitous (ub)MUNC13-2 and its binding partner, DOC2-gamma [9].
• Immunohistochemistry showed that Dab-2 immunostaining occurred in most of the vessels in the control cerebral cortex [10].

References