CAMK1D: Human Ca2+/calmodulin-dependent protein kinase I-delta
PDB Code: 2JC6
The Ser/Thr kinases Ca2+/calmodulin-dependent protein kinase I (CaMKI) constitutes a family of closely related isoforms (alpha, beta, delta and gamma). CAMK1D, also known as CKLIK is expressed in polymorphonuclear leukocytes (PMNs) and may be part of the chemokine signal transduction pathway that regulates granulocyte function. CAMK1D is enzymatically active and its activity is enhanced by Ca(2+) and calmodulin. Expression of this kinase is increases during differentiation of CD34 positive cord blood stem cells toward a neutrophilic lineage and is maximal during terminal differentiation. In addition, CAMK1D activity is induced by IL8 in myeloid cell lines stably expressing this kinase. Transfection of COS cells with constitutively active CAMK1D showed that activation of this kinase results in downstream activation of ERK1 mitogen-activated protein kinase activity.
Here we present the structure of CaMK1D in complex with the ATP competitive inhibitor(5-Methyl-1H-pyrazol-3-yl)-(2-phenylquinazolin-4-yl)amine. This inhibitor has been initially described as a potent GSK3 inhibitor with a Ki of 24 nM.
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