The CLK family kinases , CLK 1 and CLK 2 , phosphorylate and activate the tyrosine phosphatase , PTP 1B . ^^^ CLK 1 and CLK 2 phosphorylation of PTP 1B in vitro activated the phosphatase activity approximately 3 5 fold using either p nitrophenol phosphate , or tyrosine phosphorylated myelin basic protein as substrates . ^^^ Co expression of CLK 1 or CLK 2 with PTP 1B in HEK 293 cells led to a 2 fold stimulation of phosphatase activity in vivo . ^^^ Phosphorylation of PTP 1B at Ser ( 50 ) by CLK 1 or CLK 2 is responsible for its enzymatic activation . ^^^ We also show that CLK 1 and CLK 2 phosphorylate and activate the S . cerevisiae PTP 1B family member , YPTP 1 . ^^^ |