Recently, I've been reading about the MyD88 dependent signalling pathway, with particular reference to its activation in Macrophages and other cells of the immune system on recognition of a pathogen. I understand that when a PAMP (Pathogen Associated Molecular Pattern) binds with a PRR (Pattern Recognition Receptor), the receptor undergoes a conformational change, which precipitates a cascade of chemical reactions between various proteins, which eventually leads (inter alia) to the translocation of NF-κB to the nucleus, which leads to the production of cytokines. My question is about the finer points, particularly with respect to TLR1 and TLR2.
My reading suggests that these generally form a heterodimer - is this always true? Are both required for a pathogen to be recognised and an immune response produced?
Upon the pathogen binding with TLR1 (whether in a complex with TLR2 or not) what precisely happens to the receptor. I understand that MyD88 is, ultimately, recruited, but by what means?
I believe I understand everything that happens after the recruitment of MyD88, but I am less clear on everything before that. I had initially understood that the recruitment of MyD88 was the immediate next step, but other sources make reference to two proteins which I was initially unaware of: TOLLIP and TIRAP. What, if anything, is their role?
I'm still a little new to stackexchange so I apologise if this question is not up to standard, in which case, let the question simply be: 'How do TLR1/TLR2 activate the MyD88 dependent pathway?'