Functional interaction of calcium-/calmodulin-dependent protein kinase II and cytosolic phospholipase A(2)

Calcium-/calmodulin-dependent protein kinase II (CaM kinase II), a decoder of Ca2+ signals, and cytosolic phospholipase A(2) (cPLA(2)), an enzyme invo lved in arachidonate release, are involved in many physiological and pathop hysiological processes. Activation of CaM kinase Il in norepinephrine-stimu lated vascular smooth muscle cells leads to activation of cPLA(2) and arach idonic acid release. Surface plasmon resonance, mass spectrometry, and kine tic studies show that CaM kinase II binds to cPLA(2) resulting in cPLA(2) p hosphorylation on Ser-515 and an increase in its enzymatic activity. Phosph opeptide mapping studies with cPLA(2) from norepinephrine-stimulated smooth muscle cells indicates that phosphorylation of cPLA(2) on Ser-515, but not on Ser-505 or Ser-727, occurs in vivo. This novel signaling pathway for ar achidonate release is shown to be cPLA(2)-dependent by use of a recently de scribed and highly selective inhibitor of this enzyme.