Good question. It depends whether you are thinking of them as individual companies or one collection. Also saying A lot makes it sound like one thing. There are 253 companies in City A. Is that a lot or a little?

I think Guide Dog's point is well taken. If you think what is the subject and what is the verb, you are pushed towards saying "are". "253 companies" is the subject and it is plural, so that suggests "are". But... "lot" is singular, so you you are turning the 253 companies into a singular entity, a "lot". "Lot" is a collective noun and it is most definitely singular. Thus you are performing the mental trick of turning many into one. This suggests "253 companies" is a singular entity and you should use "is". Either way, you're a winner. Here's a similar example: "Ten guests for dinner is a handful!!"