AKCAKALE, Turkey — Turkey's military hit targets inside Syria on Wednesday in response to a mortar bomb fired from Syrian territory, which killed five Turkish civilians.

In the most serious cross-border escalation of the 18-month uprising in Syria, Turkey hit back at what it called "the last straw" when a mortar hit a residential neighbourhood of the border town of Akcakale.

NATO called an urgent meeting to discuss the matter.

"Our armed forces in the border region responded immediately to this abominable attack in line with their rules of engagement; targets were struck through artillery fire against places in Syria identified by radar," Prime Minister Tayyip Erdogan's office said in a statement.

"Turkey will never leave unanswered such kinds of provocation by the Syrian regime against our national security," the statement read

There were no immediate details of the Turkish strikes against Syria, nor was it clear who had fired the mortar into Turkish territory.

Residents of Akcakale gathered outside the local mayor's office, afraid to return to their homes as the dull thud of distant artillery fire rumbled across the town.

U.N. Secretary-General Ban Ki-moon had urged Turkey to keep all channels of communication open with Syria.

He later issued a statement calling on "the Syria Government to respect fully the territorial integrity of its neighbours as well as to end the violence against the Syrian people."

Secretary of State Hillary Clinton expressed outrage at the mortar from Syria and said Washington would discuss with Ankara what the next steps should be, calling the spread of violence a "very, very dangerous situation."

Washington sees Turkey as a pivotal player in backing Syria's opposition and planning for the post-Assad era. But Ankara has found itself increasingly isolated and frustrated by a lack of international consensus on how to end the conflict.

Turkey's military response contrasted with its relative restraint when Syria shot down a Turkish reconnaissance jet in June. Ankara increased its military presence along its 900-km (560-mile) border with Syria and called a meeting of NATO's North Atlantic Council.

That meeting was only the second time in NATO's 63-year history that members had convened under Article 4 of its charter which provides for consultations when a member state feels its territorial integrity, political independence or security is under threat.

The same article was invoked for the meeting of NATO ambassadors to be held in Brussels later on Wednesday.

Turkish Deputy Prime Minister Bulent Arinc said after the mortar attack: "This latest incident is the last straw. Turkey is a sovereign country. Its own soil has been attacked."

"There must be a response to this under international law," he said, according to Turkey's Cihan news agency.

Some 30,000 people have been killed across Syria, activists say, in an uprising that has grown into a full-scale civil war with sectarian overtones and threatens to draw in regional Sunni Muslim and Shiite powers.

Violence inside Syria intensified on Wednesday with three suicide car bombs and a mortar barrage ripping through a government-controlled district of central Aleppo housing a military officers' club, killing 48 people, according to activists.