 In addition, researchers have proposed a model of how A-Raf is linked to endocytosis.Upstream of A-Raf, receptor tyrosine kinases (RTKs) are activated, leading to RAS-mediated activation of Raf kinases, including A-Raf.Once activated, A-Raf binds to membranes rich in Phosphatidylinositol 4,5-bisphosphate (PtdIns (4,5)P2 and signals endosomes.