CCM2 (F8G7Z) Rabbit mAb #32463

The cerebral cavernous malformation (CCM) proteins CCM1/KRIT1, CCM2/Malcavernin, and CCM3/PDCD10 form a heterotrimeric complex critical for stabilizing endothelial cell junctions and thus blood vessel formation and vascular integrity (1). Loss of function mutations of any of the three complex members is associated with formation of CCMs, characterized by weak, inelastic, and leaky epithelium that can lead to seizures, stroke, and other neurological symptoms (2-5). CCM2 contains an N-terminal phosphotyrosine binding domain (PTB) that interacts with TrkA receptor (6), where it induces cell death in medulloblastoma cells after activation by STK25 kinase (7). CCM2 C-terminal harmonin homology domain (HHD) binds and suppresses the activity of MEKK3 kinase, and increased expression of MEKK3 target genes KLF2/KLF4 is observed in early CCM lesions (8). Gain-of-function mutations in PI3 Kinase are observed in the majority of CCM lesions (9), and these mutations synergize with CCM protein loss to increase mTOR signaling (9,10), suggesting that mTOR inhibitors may be a novel approach to treating CCM lesions.