Skip to main content
. Author manuscript; available in PMC: 2011 Jan 10.
Published in final edited form as: Immunol Rev. 2009 Nov;232(1):195–217. doi: 10.1111/j.1600-065X.2009.00834.x

Figure 2. Negative regulation of Fyn kinase by Lyn-phosphorylated Cbp/PAG.

Figure 2

The adapter Cbp is a transmembrane protein that is targeted to lipid rafts due to its palmitoylation. In mast cells (MCs), Cbp is moderately phosphorylated in resting cells by Lyn kinase and shows a moderate association with the negative regulatory kinase Csk, which phosphorylates Src PTKS and inactivates them. FcεRI stimulation greatly enhances the phosphorylation of Cbp (on Y317) in a Lyn-dependent manner. This allows additional recruitment of Csk, which phosphorylates Fyn at its C-terminal tyrosine (Y525) causing an intra-molecular folding (via interaction with its own SH2 domain) that inactivates it. This negative regulation of Fyn (and possibly of other Src PTKS) controls the responsiveness of the MC. In the absence of Lyn, MCs are hyperresponsive due to loss of this negative regulatory mechanism.