| Soluble Axl is generated by ADAM 10 dependent cleavage and associates with Gas 6 in mouse serum . ^^^ We show that constitutive and phorbol 12 myristate 13 acetate induced generation of soluble Axl ( sAxl ) involves the activity of disintegrin like metalloproteinase 10 ( ADAM 10 ) . ^^^ Spontaneous and inducible Axl cleavage was inhibited by the broad spectrum metalloproteinase inhibitor GM 6001 and by hydroxamate GW280264X , which is capable of blocking ADAM 10 and ADAM 17 . ^^^ Furthermore , murine fibroblasts deficient in ADAM 10 expression exhibited a significant reduction in constitutive and inducible Axl shedding , whereas reconstitution of ADAM 10 restored sAxl production , suggesting that ADAM 10 mediated proteolysis constitutes a major mechanism for sAxl generation in mice . ^^^ |