“Sure. What's up?”

One of the people who works under you came to your office to ask a question. He asked you "Can I ask you something?" You were typing an email, but it wasn't that important, so you answer him like this.

Sure. What's up?

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"Sure" means "yes".

A: Hey, can you help me with this?

B: Sure.

 But "sure" is more casual than "yes".

If you just answer "yes" to a question, it can sound as if you are angry:

A: Hey, can you help me with this?

B: Yes.

A: Uh... Are you annoyed or something?

"Sure" is similar to "of course". Both suggest that it's obvious and expected for the answer to be "yes".

A: Will you come to my graduation?

B: Of course!

"Of course" is a stronger response and more positive response than "sure".

What's up?

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?