You can use the phrase "What's up?" in many different ways. One of its uses is to respond when someone asks to talk with you:
A: Hey, can I talk with you for a minute?
B: Yeah, what's up?
"What's up?" sounds light and casual. You can use this phrase with people who you work closely with, who you're friends with, or who work for you.
A more formal alternative to "What's up? is:
What can I do for you?
Or, if the person you're talking to seems upset, you can ask:
What's going on?