Abstract
Cardiac-restricted genes play important roles in cardiovascular system. In an effort to identify such novel genes we identified a novel cardiac-specific kinase gene TNNI3K localized on 1p31.1 based on bioinformatics analyses. Sequence analysis suggested that TNNI3K is a distant family member of integrin-linked kinase. Northern blot and 76-tissue array analyses showed that TNNI3K is highly expressed in heart, but is undetectable in other tissues. Immunohistochemical analysis predominantly localized TNNI3K in the nucleus of cardiac myocytes. In vitro kinase assay showed that TNNI3K is a functional kinase. The yeast two-hybrid system showed that TNNI3K could directly interact with cardiac troponin I, results that were further confirmed by coimmunoprecipitation in vivo. Our data suggest that TNNI3K is a cardiac-specific kinase and play important roles in cardiac system.
Similar content being viewed by others
Abbreviations
- Ab :
-
Antibody
- cTnI :
-
Cardiac troponin I
- ILK :
-
Integrin-linked kinase
- SDS:
-
Sodium dodecyl sulfate
References
Dempsey AA, Dzau VJ, Liew CC (2001) Cardiovascular genomics: estimating the total number of genes expressed in the human cardiovascular system. J Mol Cell Cardiol 33:1879–1886
Towbin JA, Bowles NE (2002) The failing heart. Nature 415:227–33
Nicol RL, Frey N, Olson EN (2000) From the sarcomere to the nucleus: role of genetics and signaling in structural heart disease. Annu Rev Genomics Hum Genet 1:179–223
Solaro RJ, Rarick HM (1998) Troponin and tropomyosin: proteins that switch on and tune in the activity of cardiac myofilaments. Circ Res 83:471–480
Solaro RJ, Van Eyk J (1996) Altered interactions among thin filament proteins modulate cardiac function. J Mol Cell Cardiol 28:217–230
Marian AJ, Roberts R (2001) The molecular genetic basis for hypertrophic cardiomyopathy. J Mol Cell Cardiol 33:655–670
Seidman JG, Seidman C (2001) The genetic basis for cardiomyopathy: from mutation identification to mechanistic paradigms. Cell 104:557–567
Chien KR (2000) Genomic circuits and the integrative biology of cardiac diseases. Nature 407:227–232
Shai SY, Harpf AE, Babbitt CJ, Jordan MC, Fishbein MC, Chen J, Omura M, Leil TA, Becker KD, Jiang M, Smith DJ, Cherry SR, Loftus JC, Ross RS (2002) Cardiac myocyte-specific excision of the beta1 integrin gene results in myocardial fibrosis and cardiac failure. Circ Res 90:458–464
Ross RS, Pham C, Shai SY, Goldhaber JI, Fenczik C, Glembotski CC, Ginsberg MH, Loftus JC (1998) Beta1 integrins participate in the hypertrophic response of rat ventricular myocytes. Circ Res 82:1160–1172
Hannigan GE, Leung-Hagesteijn C, Fitz-Gibbon L, Coppolino MG, Radeva G, Filmus J, Bell JC, Dedhar S (1996) Regulation of cell adhesion and anchorage-dependent growth by a new beta 1-integrin-linked protein kinase. Nature 379:91–96
Dedhar S (2000) Cell-substrate interactions and signaling through ILK. Curr Opin Cell Biol 12:250–256
Wei YJ, Ding JF, Zhao Y, Wang XR, Liu YQ, Xu YY, Xiong H, Zhou Y, Hui RT, Gao RL, Qiang BQ (1999) Construction of human adult artery and heart cDNA libraries and cloning of novel full-length cDNAs. Chinese Circ J 14:369–371
Zhao Y, Wei YJ, Cao HQ, Ding JF (2001) Molecular cloning of NELIN, a putative human cytoskeleton regulation gene. Acta Biochim Biophys Sina 33:19–24
Horton RM, Hunt HD, Ho SN, Pullen JK, Pease LR (1989) Engineering hybrid genes without the use of restriction enzymes: gene splicing by overlap extension. Gene 77:61–68
Diener K, Wang XS, Chen C, Meyer CF, Keesler G, Zukowski M, Tan TH, Yao Z (1997) Activation of the c-Jun N-terminal kinase pathway by a novel protein kinase related to human germinal center kinase. Proc Natl Acad Sci U S A 94:9687–9692
Burnett PE, Blackshaw S, Lai MM, Qureshi IA, Burnett AF, Sabatini DM, Snyder SH (1998) Neurabin is a synaptic protein linking p70 S6 kinase and the neuronal cytoskeleton. Proc Natl Acad Sci U S A 95:8351–8356
Hanks SK, Quinn AM, Hunter T (1988) The protein kinase family: conserved features and deduced phylogeny of the catalytic domains. Science 241:42–52
Hanks SK, Hunter T (1995) Protein kinases 6, The eukaryotic protein kinase superfamily: kinase (catalytic) domain structure and classification. FASEB J 9:576–596
Sakuma H, Ikeda A, Oka S, Kozutsumi Y, Zanetta JP, Kawasaki T (1997) Molecular cloning and functional expression of a cDNA encoding a new member of mixed lineage protein kinase from human brain. J Biol Chem 272:28622–28629
Huang Y, Li J, Zhang Y, Wu C (2000) The roles of integrin-linked kinase in the regulation of myogenic differentiation. J Cell Biol 150:861–872
Brott BK, Pinsky BA, Erikson RL (1998) Nlk is a murine protein kinase related to Erk/MAP kinases and localized in the nucleus. Proc Natl Acad Sci U S A 95:963–968
Solaro RJ (1999) Troponin, I stunning, hypertrophy, and failure of the heart. Circ Res 84:122–124
Swynghedauw B (1999) Molecular mechanisms of myocardial remodeling. Physiol Rev 79:215–262
Manning G, Whyte DB, Martinez R, Hunter T, Sudarsanam S (2002) The protein kinase complement of the human genome. Science 298:1912–1934
Acknowledgements
We are grateful to Prof. Jian Tang's assistance in generation of polyclonal antibodies against TNNI3K and Prof. Boqin Olang and Prof. Minshun Zhao's help in many respects. This work was supported by the National Natural Science Foundation of China (no. 30070313) and National 973 Project of China (no. G2000056901).
Author information
Authors and Affiliations
Corresponding author
Additional information
The nucleotide sequence reported here has been deposited in the GenBank database under GenBank accession number AF116826. The gene symbol TNNI3K has been approved by the HUGO Gene Nomenclature Committee
Rights and permissions
About this article
Cite this article
Zhao, Y., Meng, XM., Wei, YJ. et al. Cloning and characterization of a novel cardiac-specific kinase that interacts specifically with cardiac troponin I. J Mol Med 81, 297–304 (2003). https://doi.org/10.1007/s00109-003-0427-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00109-003-0427-x