| | Re: SHP1 and Phosphotyrosine in NK
A Toll-like receptor (TLR) bound to ligand recruits TIR-containing adaptor molecules leading to a signal cascade to activate NF-κB. After TNF receptor binding to FADD and TRADD, TRAF family members (TRAF2, 5, and 6), and the kinase RIP1. The TRAF/RIP complex recruits and activates TAK1, which induces activation of the IKK complex and downstream signaling via the NF-κB pathway. NF-κB plays an important role in chromatin remodeling. Unphosphorylated p65-containing NF-κB heterodimers or p50 homodimers bind to repressive histone deacetylases (HDACs) and suppress transcription. In the cytoplasm, p65 can be phosphorylated by IKK and protein kinase A (PKA), and in the nucleus by MSK1. Phosphorylation of histones by IKKα or MSK1 directly promote transcription.