 All genes known so far to be linked to HHT code for proteins in the TGF @-@ β signaling pathway . This is a group of proteins that participates in signal transduction of hormones of the transforming growth factor beta superfamily ( the transforming growth factor beta , bone morphogenetic protein and growth differentiation factor classes ) , specifically BMP9 / GDF2 and BMP10 . The hormones do not enter the cell but link to receptors on the cell membrane ; these then activate other proteins , eventually influencing cellular behavior in a number of ways such as cellular survival , proliferation ( increasing in number ) and differentiation ( becoming more specialized ) . For the hormone signal to be adequately transduced , a combination of proteins is needed : two each of two types of serine / threonine @-@ specific kinase type membrane receptors and endoglin . When bound to the hormone , the type II receptor proteins phosphorylate ( transfer phosphate ) onto type I receptor proteins ( of which Alk @-@ 1 is one ) , which in turn phosphorylate a complex of SMAD proteins ( chiefly SMAD1 , SMAD5 and SMAD8 ) . These bind to SMAD4 and migrate to the cell nucleus where they act as transcription factors and participate in the transcription of particular genes . In addition to the SMAD pathway , the membrane receptors also act on the MAPK pathway , which has additional actions on the behavior of cells . Both Alk @-@ 1 and endoglin are expressed predominantly in endothelium , perhaps explaining why HHT @-@ causing mutations in these proteins lead predominantly to blood vessel problems . Both ENG and ACVRL1 mutations lead predominantly to underproduction of the related proteins , rather than misfunctioning of the proteins . 
