After I re-install I have the issue that SHIFT+E+2 does no longer open up cargo doors on planes like the POSKY 777s or the Wilco/Feelthere ERJs. SHIFT + E works without any problem. I have not assigned the key combination to another command. So what am I doing wrong or missing?

Well I would change the key assignment of Shift + E to just D (for door) for starters......makes life a lot easier.

Yes a common FS9 issue. Search the Avsim database for this file: cx_cargo_door.zip It requires a quick edit in your panel.cfg but it will place a button on the GPS which will open the extra doors every time! Works for me! Used it for years... edetroit's method won't help as it is an internal FS9 issue and not a button assignment issue. But I could be wrong...