Multifunctional calmodulin-dependent kinases

Saitoh, Y., Yamamoto, H., Fukunaga, K., Matsukado, Y. and Miyamoto, E., 1987, Inactivation and reactivation of the multifunctional calmodulin-dependent protein kinase from brain by autophosphorylation and dephosphorylation Involvement of protein phosphatases from brain, Journal of Neurochemistry, 49, pp 1286—1292. 

Braun, A.E and Schulman, H. The multifunctional caldum/calmodulin dependent protein kinase From form to function (1995) Annu. Rev. Physiol. 57, 417-445... 

Additional information <1> (<1> isozyme of calmodulin-dependent multifunctional protein kinase II in smooth-muscle [5] <1> caldesmon is not a substrate of smooth-muscle myosin light-chain kinase [3] <1> no substrates are bovine cardiac C-protein, bovine brain fodrin, rabbit skeletal muscle glycogen synthase, phosphorylase B, troponon (I -I- T -I- C), actin, tropomyosin, smooth-muscle actin, filamin, vinculin, cr-actinin, protamine or phosvitin [1]) [1-3]... 

Ikebe, M. Reardon, S. Scott-Woo, G.C. Zhou, Z. Koda, Y. Purification and characterization of calmodulin-dependent multifunctional protein kinase from smooth muscle isolation of caldesmon kinase. Biochemistry, 29, 11242-11248 (1990)... 

Schulman, H. Kuret, J. Bennett Jefferson, A. Nose, P.S. Spitzer, K.H. Ca " / calmodulin-dependent microtubule-associated protein 2 kinase broad substrate specificity and multifunctional potential in diverse tissues. Biochemistry, 24, 5320-5327 (1985)... 

Cruzalegui, F. H. and Means, A. R., 1993, Biochemical characterization of the multifunctional Ca2+/calmodulin-dependent protein kinase type IV expressed in insect cells, J Biol Chem, 268, pp 26171-26178. 

Anderson, M.E., Braun, A.P., Schulman, H., et al., 1994, Multifunctional Ca2+/calmodulin-dependent protein kinase mediates Ca(2+)-induced enhancement of the L-type Ca2+ current in rabbit ventricular myocytes. Circ Res, 75(5), pp 854—61. 

Fujisawa H. (2001) Regulation of the activities of multifunctional Ca2+/calmodulin-dependent protein kinases. J Biochem (Tokyo). 129, 193-9. 

Multifunctional Ca2+/calmodulin-dependent protein kinase Domain structure and regulation, H. Schulman and L. 

It was originally recognised by Dabrowska et al. (1978) that calmodulin was part of the active holoenzyme MLCK complex. The association of calmodulin with MLCK is rapid and appears to be diffusion limited. It could be described by a two-step process, a bimolecular step and an isomerisation (Torok and Trentham 1994). The time required for activating MLCK by Ca +/calmodulin may contribute to the latency of about 400-500 ms at 37 C which precedes increases in LC20 phosphorylation (Miller-Hance et al. 1988). The interaction of Ca Vcalmodulin with MLCK may be modulated by phosphorylation of MLCK. Purified MLCK is a substrate for protein kinase A (Conti and Adelstein 1981), the multifunctional Ca /calmodulin dependent protein kinase II (Hashimoto and Soderling 1990, Ikebe and Reardon 1990), protein kinase C (PKC) (Nishikawa et al. 1983) and mitogen activated protein kinase (MAP kinase, Klemke et al. 1997). Phosphorylation of MLCK by these protein kinases may alter the Ca -sensitivity of the enzyme and hence of contraction, as will be discussed below. 

Ikebe M, Reardon S (1990) Phosphorylation of smooth myosin light chain kinase by smooth muscle Ca " /calmodulin-dependent multifunctional protein kinase. J Biol Chem 265 8975-8978... 

Other studies have demonstrated that the skeletal muscle ai peptide can be phosphorylated in T-tubule membranes by a multifunctional Ca " /calmodulin (CaM)-dependent protein kinase [111], Phosphorylation occurs on the i subunit to an extent of 2 mol phosphate/mol subunit and on the /i subunit to an extent of 0.7-1 mol phosphate/mol channel [108,111]. Phosphorylation catalyzed by the CaM-kinase on the ai subunit is additive to that caused by PKA and occurs on distinct sites [111]. So far, however, we have not observed any functional consequences of phosphorylation of the skeletal muscle Ca channels by the CaM-kinase. 

---