Question

What is the type of interaction occurring between K-Ras and Raf. Explain. (cell-signalling)

Answer 1

Answer- Downstream of RAS, mammalian cells express three RAF paralogs (ARAF, BRAF, and CRAF) that share a conserved C-terminal kinase domain (KD). They also comprise an N-terminal regulatory region (NTR) consisting of a RAS-binding domain (RBD), a cysteine-rich domain (CRD), and a Ser/Thr-rich region. The mammalian RAF family also comprises two KSR isoforms that share significant sequence identity with RAF proteins in their C-terminal kinase domain and present a related NTR organization with the exception that they contain a signature domain, called the coiled coil-sterile α motif (CC-SAM) domain, and lack an RBD domain1. In unstimulated cells, RAF proteins are sequestered in the cytoplasm as monomers in an autoinhibited state through an intramolecular interaction between their NTR and kinase domain. Upon RTK activation, GTP-bound RAS binds to the RAF RBD, which is thought to release the NTR−KD interaction. This event is accompanied by dephosphorylation of inhibitory sites and phosphorylation of activating residues that respectively contribute to membrane anchoring and kinase domain activation. Concomitantly, RAF proteins undergo kinase domain side-to-side dimerization. This step allosterically drives catalytic switching to the ON-state and is essential for kinase domain activation. Here we refer to the ON-state as dimeric full-length RAF in which NTR autoinhibition has been relieved. Activated RAF proteins convey signals by initiating a phosphorylation cascade from RAF to MEK and MEK to ERK, which culminates in the phosphorylation of an array of substrates eliciting cell-specific responses.