FIGURE 9.

Proposed model for the regulation of SHIP2 monoubiquitination. At short times of EGF stimulation (5 min), SHIP2 would be protected from monoubiquitination due to the integrity of its SH2 domain, which could be engaged in an intramolecular interaction with an internal phosphorylated tyrosine or through interaction with a phosphorylated tyrosine of a proteic partner. After longer EGF stimulation times (30 min), disruption of the intramolecular interaction, caused by decreasing of SHIP2 tyrosine phosphorylation, or disruption of interaction with a partner would allow the accessibility of the monoubiquitination site and favor the SHIP2 monoubiquitination. The labels used are as follows: SH2, SHIP2 SH2 domain; K315, lysine on position 315 in SHIP2; and pY, phosphorylated tyrosine.