Labour MP Tristram Hunt is quitting as an MP to become the director of London's Victoria and Albert Museum, triggering a by-election.
Mr Hunt told the BBC that while he had "had differences" with party leader Jeremy Corbyn in the past "that wasn't the spur" for stepping down.
"The spur was the incredible opportunity of the job," he said.
Labour leader Mr Corbyn said he wished him well and was confident Labour would hold the Stoke-on-Trent Central seat.
Asked if he was secretly pleased that an MP who has been critical of his leadership was going, Mr Corbyn said: "No, I don't want anyone to resign, I don't want to lose MPs but he has taken this position as director of the V&A, good luck to him."
'Frustration'
He said he was confident of winning the by-election: "It's been a Labour seat for a long time, we have a strong message to put out .. I'm looking forward to the campaign."
Mr Hunt is the second Labour MP in a matter of weeks to quit Parliament for a job outside politics. Jamie Reed announced last month he was standing down as MP for Copeland to take up a post at the Sellafield nuclear plant.
Mr Hunt's departure sets up another potentially awkward by-election for Mr Corbyn, in a traditionally safe Labour seat where UKIP made a strong showing in the last general election. The seat is set to be abolished under new boundary proposals.
Labour grandee Lord Mandelson said he believed Mr Hunt quit politics because he was "unhappy", like "many other MPs" over Labour's electoral chances.
"The prospects of us winning a national general election will remain distant the longer Jeremy Corbyn and his ramshackle outfit remain in charge of the party's fortunes," he told the BBC's Week in Westminster.
'Plain wrong'
In a letter to local party members explaining his decision, Mr Hunt said: "I am sorry to put you, the party and the people of Stoke-on-Trent, through a by-election. I have no desire to rock the boat now and anyone who interprets my decision to leave in that way is just plain wrong."
The former TV historian was elected to represent Stoke-on-Trent in 2010 and was re-elected in 2015 with a majority of 5,179. UKIP came second.
He refused to serve in the shadow cabinet following Mr Corbyn's leadership victory in September 2015. He also argued that the Labour leader should have done more to persuade its voters to back the Remain campaign during last year's EU referendum.
Stoke-on-Trent Central
- Labour has held the seat since its creation in 1950
- The constituency has a majority of working class residents and is wholly urban
- Mr Hunt won comfortably in 2010 and 2015
- But owing to low turnout just 19% of his constituents voted for him, making him "Britain's most unpopular MP" (New Statesman)
- The seat was the only one in the 2015 general election where the majority of the electorate did not vote (49.9% did so)
- The seat has higher unemployment than the national average due to the closure of heavy industries in recent years.
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