One of the SH2 domains binds to the catalytic domain of SHP-2, to prevent SHP-2 functioning.[3] Then, when a protein with a phosphorylated tyrosine binds, the SH2 domain changes orientation and SHP-2 is activated.[33] SHP-2 is then able to remove phosphate groups from JAKs, STATs and the receptors themselves - so, like SHP-1, can prevent the phosphorylation needed for the pathway to continue, and therefore inhibit JAK-STAT signalling.