Abstract
Six variants of calmodulin-dependent protein kinase IIgamma were isolated from a ferret-aorta smooth-muscle cDNA library. Variant G-2 is generated by a novel alternative polyadenylation, utilizing a site contained in an intron. The last 77 residues of the association domain are replaced with 99 residues of a unique sequence containing Src homology 3-domain-binding motifs, which alter catalytic activity. Variant C-2 has an eight-residue deletion in an ATP-binding motif and does not autophosphorylate Thr(286), but does phosphorylate exogenous substrate. Two variants, B and J, autodephosphorylate. Four variants differing only in the variable domain have differing catalytic activities, despite identical sequences in the catalytic domains. Thus structural features determined by variable and association domains are important for the catalytic activity of calmodulin-dependent protein kinase II.
Full Text
The Full Text of this article is available as a PDF (319.7 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bairoch A., Claverie J. M. Sequence patterns in protein kinases. Nature. 1988 Jan 7;331(6151):22–22. doi: 10.1038/331022a0. [DOI] [PubMed] [Google Scholar]
- Braun A. P., Schulman H. The multifunctional calcium/calmodulin-dependent protein kinase: from form to function. Annu Rev Physiol. 1995;57:417–445. doi: 10.1146/annurev.ph.57.030195.002221. [DOI] [PubMed] [Google Scholar]
- Breitbart R. E., Andreadis A., Nadal-Ginard B. Alternative splicing: a ubiquitous mechanism for the generation of multiple protein isoforms from single genes. Annu Rev Biochem. 1987;56:467–495. doi: 10.1146/annurev.bi.56.070187.002343. [DOI] [PubMed] [Google Scholar]
- Colbran R. J., Soderling T. R. Calcium/calmodulin-independent autophosphorylation sites of calcium/calmodulin-dependent protein kinase II. Studies on the effect of phosphorylation of threonine 305/306 and serine 314 on calmodulin binding using synthetic peptides. J Biol Chem. 1990 Jul 5;265(19):11213–11219. [PubMed] [Google Scholar]
- Edelman A. M., Lin W. H., Osterhout D. J., Bennett M. K., Kennedy M. B., Krebs E. G. Phosphorylation of smooth muscle myosin by type II Ca2+/calmodulin-dependent protein kinase. Mol Cell Biochem. 1990 Sep 3;97(1):87–98. doi: 10.1007/BF00231704. [DOI] [PubMed] [Google Scholar]
- Edwalds-Gilbert G., Veraldi K. L., Milcarek C. Alternative poly(A) site selection in complex transcription units: means to an end? Nucleic Acids Res. 1997 Jul 1;25(13):2547–2561. doi: 10.1093/nar/25.13.2547. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ghosh A., Greenberg M. E. Calcium signaling in neurons: molecular mechanisms and cellular consequences. Science. 1995 Apr 14;268(5208):239–247. doi: 10.1126/science.7716515. [DOI] [PubMed] [Google Scholar]
- Greenwood I. A., Ledoux J., Leblanc N. Differential regulation of Ca(2+)-activated Cl(-) currents in rabbit arterial and portal vein smooth muscle cells by Ca(2+)-calmodulin-dependent kinase. J Physiol. 2001 Jul 15;534(Pt 2):395–408. doi: 10.1111/j.1469-7793.2001.00395.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Guntaka R. V. Transcription termination and polyadenylation in retroviruses. Microbiol Rev. 1993 Sep;57(3):511–521. doi: 10.1128/mr.57.3.511-521.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hanks S. K., Hunter T. Protein kinases 6. The eukaryotic protein kinase superfamily: kinase (catalytic) domain structure and classification. FASEB J. 1995 May;9(8):576–596. [PubMed] [Google Scholar]
- Hanson P. I., Meyer T., Stryer L., Schulman H. Dual role of calmodulin in autophosphorylation of multifunctional CaM kinase may underlie decoding of calcium signals. Neuron. 1994 May;12(5):943–956. doi: 10.1016/0896-6273(94)90306-9. [DOI] [PubMed] [Google Scholar]
- Hanson P. I., Schulman H. Inhibitory autophosphorylation of multifunctional Ca2+/calmodulin-dependent protein kinase analyzed by site-directed mutagenesis. J Biol Chem. 1992 Aug 25;267(24):17216–17224. [PubMed] [Google Scholar]
- Hanson P. I., Schulman H. Neuronal Ca2+/calmodulin-dependent protein kinases. Annu Rev Biochem. 1992;61:559–601. doi: 10.1146/annurev.bi.61.070192.003015. [DOI] [PubMed] [Google Scholar]
- Hudmon Andy, Schulman Howard. Neuronal CA2+/calmodulin-dependent protein kinase II: the role of structure and autoregulation in cellular function. Annu Rev Biochem. 2001 Nov 9;71:473–510. doi: 10.1146/annurev.biochem.71.110601.135410. [DOI] [PubMed] [Google Scholar]
- Hudmon Andy, Schulman Howard. Structure-function of the multifunctional Ca2+/calmodulin-dependent protein kinase II. Biochem J. 2002 Jun 15;364(Pt 3):593–611. doi: 10.1042/BJ20020228. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Je H. D., Gangopadhyay S. S., Ashworth T. D., Morgan K. G. Calponin is required for agonist-induced signal transduction--evidence from an antisense approach in ferret smooth muscle. J Physiol. 2001 Dec 1;537(Pt 2):567–577. doi: 10.1111/j.1469-7793.2001.00567.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kamps M. P., Taylor S. S., Sefton B. M. Direct evidence that oncogenic tyrosine kinases and cyclic AMP-dependent protein kinase have homologous ATP-binding sites. Nature. 1984 Aug 16;310(5978):589–592. doi: 10.1038/310589a0. [DOI] [PubMed] [Google Scholar]
- Kanaseki T., Ikeuchi Y., Sugiura H., Yamauchi T. Structural features of Ca2+/calmodulin-dependent protein kinase II revealed by electron microscopy. J Cell Biol. 1991 Nov;115(4):1049–1060. doi: 10.1083/jcb.115.4.1049. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kim I., Je H. D., Gallant C., Zhan Q., Riper D. V., Badwey J. A., Singer H. A., Morgan K. G. Ca2+-calmodulin-dependent protein kinase II-dependent activation of contractility in ferret aorta. J Physiol. 2000 Jul 15;526(Pt 2):367–374. doi: 10.1111/j.1469-7793.2000.00367.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kim S. A., Hudmon A., Volmer A., Waxham M. N. CaM-kinase II dephosphorylates Thr(286) by a reversal of the autophosphorylation reaction. Biochem Biophys Res Commun. 2001 Apr 6;282(3):773–780. doi: 10.1006/bbrc.2001.4651. [DOI] [PubMed] [Google Scholar]
- Knighton D. R., Zheng J. H., Ten Eyck L. F., Ashford V. A., Xuong N. H., Taylor S. S., Sowadski J. M. Crystal structure of the catalytic subunit of cyclic adenosine monophosphate-dependent protein kinase. Science. 1991 Jul 26;253(5018):407–414. doi: 10.1126/science.1862342. [DOI] [PubMed] [Google Scholar]
- Kolb S. J., Hudmon A., Ginsberg T. R., Waxham M. N. Identification of domains essential for the assembly of calcium/calmodulin-dependent protein kinase II holoenzymes. J Biol Chem. 1998 Nov 20;273(47):31555–31564. doi: 10.1074/jbc.273.47.31555. [DOI] [PubMed] [Google Scholar]
- Kolodziej S. J., Hudmon A., Waxham M. N., Stoops J. K. Three-dimensional reconstructions of calcium/calmodulin-dependent (CaM) kinase IIalpha and truncated CaM kinase IIalpha reveal a unique organization for its structural core and functional domains. J Biol Chem. 2000 May 12;275(19):14354–14359. doi: 10.1074/jbc.275.19.14354. [DOI] [PubMed] [Google Scholar]
- Lengyel I., Nairn A., McCluskey A., Tóth G., Penke B., Rostas J. Auto-inhibition of Ca(2+)/calmodulin-dependent protein kinase II by its ATP-binding domain. J Neurochem. 2001 Feb;76(4):1066–1072. doi: 10.1046/j.1471-4159.2001.00139.x. [DOI] [PubMed] [Google Scholar]
- Lin C. R., Kapiloff M. S., Durgerian S., Tatemoto K., Russo A. F., Hanson P., Schulman H., Rosenfeld M. G. Molecular cloning of a brain-specific calcium/calmodulin-dependent protein kinase. Proc Natl Acad Sci U S A. 1987 Aug;84(16):5962–5966. doi: 10.1073/pnas.84.16.5962. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lorca T., Abrieu A., Means A., Dorée M. Ca2+ is involved through type II calmodulin-dependent protein kinase in cyclin degradation and exit from metaphase. Biochim Biophys Acta. 1994 Sep 29;1223(3):325–332. doi: 10.1016/0167-4889(94)90091-4. [DOI] [PubMed] [Google Scholar]
- McCarron J. G., McGeown J. G., Reardon S., Ikebe M., Fay F. S., Walsh J. V., Jr Calcium-dependent enhancement of calcium current in smooth muscle by calmodulin-dependent protein kinase II. Nature. 1992 May 7;357(6373):74–77. doi: 10.1038/357074a0. [DOI] [PubMed] [Google Scholar]
- Menice C. B., Hulvershorn J., Adam L. P., Wang C. A., Morgan K. G. Calponin and mitogen-activated protein kinase signaling in differentiated vascular smooth muscle. J Biol Chem. 1997 Oct 3;272(40):25157–25161. doi: 10.1074/jbc.272.40.25157. [DOI] [PubMed] [Google Scholar]
- Morris E. P., Török K. Oligomeric structure of alpha-calmodulin-dependent protein kinase II. J Mol Biol. 2001 Apr 20;308(1):1–8. doi: 10.1006/jmbi.2001.4584. [DOI] [PubMed] [Google Scholar]
- Morrison D. L., Sanghera J. S., Stewart J., Sutherland C., Walsh M. P., Pelech S. L. Phosphorylation and activation of smooth muscle myosin light chain kinase by MAP kinase and cyclin-dependent kinase-1. Biochem Cell Biol. 1996;74(4):549–557. doi: 10.1139/o96-459. [DOI] [PubMed] [Google Scholar]
- Nghiem P., Saati S. M., Martens C. L., Gardner P., Schulman H. Cloning and analysis of two new isoforms of multifunctional Ca2+/calmodulin-dependent protein kinase. Expression in multiple human tissues. J Biol Chem. 1993 Mar 15;268(8):5471–5479. [PubMed] [Google Scholar]
- Nguyen D. H., Catling A. D., Webb D. J., Sankovic M., Walker L. A., Somlyo A. V., Weber M. J., Gonias S. L. Myosin light chain kinase functions downstream of Ras/ERK to promote migration of urokinase-type plasminogen activator-stimulated cells in an integrin-selective manner. J Cell Biol. 1999 Jul 12;146(1):149–164. doi: 10.1083/jcb.146.1.149. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Patton B. L., Miller S. G., Kennedy M. B. Activation of type II calcium/calmodulin-dependent protein kinase by Ca2+/calmodulin is inhibited by autophosphorylation of threonine within the calmodulin-binding domain. J Biol Chem. 1990 Jul 5;265(19):11204–11212. [PubMed] [Google Scholar]
- Proudfoot N. Connecting transcription to messenger RNA processing. Trends Biochem Sci. 2000 Jun;25(6):290–293. doi: 10.1016/s0968-0004(00)01591-7. [DOI] [PubMed] [Google Scholar]
- Singer H. A., Benscoter H. A., Schworer C. M. Novel Ca2+/calmodulin-dependent protein kinase II gamma-subunit variants expressed in vascular smooth muscle, brain, and cardiomyocytes. J Biol Chem. 1997 Apr 4;272(14):9393–9400. doi: 10.1074/jbc.272.14.9393. [DOI] [PubMed] [Google Scholar]
- Soderling T. R., Stull J. T. Structure and regulation of calcium/calmodulin-dependent protein kinases. Chem Rev. 2001 Aug;101(8):2341–2352. doi: 10.1021/cr0002386. [DOI] [PubMed] [Google Scholar]
- Takeuchi M., Fujisawa H. New alternatively spliced variants of calmodulin-dependent protein kinase II from rabbit liver. Gene. 1998 Oct 9;221(1):107–115. doi: 10.1016/s0378-1119(98)00422-3. [DOI] [PubMed] [Google Scholar]
- Tobimatsu T., Fujisawa H. Tissue-specific expression of four types of rat calmodulin-dependent protein kinase II mRNAs. J Biol Chem. 1989 Oct 25;264(30):17907–17912. [PubMed] [Google Scholar]
- Tobimatsu T., Kameshita I., Fujisawa H. Molecular cloning of the cDNA encoding the third polypeptide (gamma) of brain calmodulin-dependent protein kinase II. J Biol Chem. 1988 Nov 5;263(31):16082–16086. [PubMed] [Google Scholar]
- Tombes R. M., Krystal G. W. Identification of novel human tumor cell-specific CaMK-II variants. Biochim Biophys Acta. 1997 Mar 1;1355(3):281–292. doi: 10.1016/s0167-4889(96)00141-3. [DOI] [PubMed] [Google Scholar]
- Yamauchi T., Ohsako S., Deguchi T. Expression and characterization of calmodulin-dependent protein kinase II from cloned cDNAs in Chinese hamster ovary cells. J Biol Chem. 1989 Nov 15;264(32):19108–19116. [PubMed] [Google Scholar]
- Yang E., Schulman H. Structural examination of autoregulation of multifunctional calcium/calmodulin-dependent protein kinase II. J Biol Chem. 1999 Sep 10;274(37):26199–26208. doi: 10.1074/jbc.274.37.26199. [DOI] [PubMed] [Google Scholar]
- Zhao J., Hyman L., Moore C. Formation of mRNA 3' ends in eukaryotes: mechanism, regulation, and interrelationships with other steps in mRNA synthesis. Microbiol Mol Biol Rev. 1999 Jun;63(2):405–445. doi: 10.1128/mmbr.63.2.405-445.1999. [DOI] [PMC free article] [PubMed] [Google Scholar]