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?