Question about appointments to Cabinet positions

Going on the premise that Kerry wins.

If he picks a sitting Senator for a high position (Cabinet, etc.), will that Senator have to resign/step down from the Senate to accept the position (if approved)?

Which is why it's a terrible idea to nominate a sitting Dem Senator to any executive branch position, unless the Governor of the state is a Dem who will name a Dem to replace him/her.

I had the thought that Kerry might be able to pull a power play by offering a post to a non-lockstep Repub senator who is in a state which has a Dem governor.

Specter is often cited as a liberal-leaner, and PA has a Dem gov.

McCain might not actually break with the party, but might salivate at the idea of a bigger power, and Arizona has a Dem gov.

Not sure of the levels of any of the following, but, along with the above, these are facing re-elections this year. If they are re-elected, the balance of power could be tipped by just one appointment.

Grassley - hasn't he shown some disgust with Bush lately?

Brownback's no possible chance in hell, since he's also attacking Stern for turning against Bush.

Nickles, Bond, Fitzgerald, I don't know their records. How likely?