CAMK1d, Active

Calcium/calmodulin-dependent protein kinase ID (CAMK1D), or a novel Ca2+/calmodulin-dependent kinase I-like kinase (CKLiK), showed kinase activity and that the activity was enhanced by Ca(2+) and calmodulin. Using a novel antibody generated against the C-terminus of CKLiK, CKLiK was detected in CD34+-derived neutrophils and eosinophils, as well as in mature peripheral blood granulocytes. Activation of human granulocytes by N-formyl-methionyl-leucyl-phenylalanine (fMLP) and platelet-activating factor (PAF), but not the phorbol ester PMA (phorbol 12-myristate-13-acetate), resulted in induction of CKLiK activity, in parallel with a rise of intracellular [Ca2+]. Furthermore, fMLP-induced neutrophil migration on albumin-coated surfaces was perturbed, as well as β2-integrin-mediated adhesion. These findings suggest a critical role for CKLiK in modulating chemoattractant-induced functional responses in human granulocytes (1). Also, CAMK1D exhibits Ca(2+)/CaM-dependent activity that is enhanced (approximately 30-fold) in vitro by phosphorylation of its Thr180 by CaM-K kinase (CaM-KK)α, consistent with detection of CAMK1D-activating activity in HeLa cells. Transiently expressed CAMK1D exhibited enhanced protein kinase activity in HeLa cells without ionomycin stimulation. This sustained activation of CAMK1D was completely abolished by Thr180Ala mutation and inhibited by CaM-KK inhibitor, STO-609, indicating a functional CaM-KK/ CAMK1D cascade in HeLa cells.