4fg9

Structural highlights

Function

KCC1A_HUMAN Calcium/calmodulin-dependent protein kinase that operates in the calcium-triggered CaMKK-CaMK1 signaling cascade and, upon calcium influx, regulates transcription activators activity, cell cycle, hormone production, cell differentiation, actin filament organization and neurite outgrowth. Recognizes the substrate consensus sequence [MVLIF]-x-R-x(2)-[ST]-x(3)-[MVLIF]. Regulates axonal extension and growth cone motility in hippocampal and cerebellar nerve cells. Upon NMDA receptor-mediated Ca(2+) elevation, promotes dendritic growth in hippocampal neurons and is essential in synapses for full long-term potentiation (LTP) and ERK2-dependent translational activation. Downstream of NMDA receptors, promotes the formation of spines and synapses in hippocampal neurons by phosphorylating ARHGEF7/BETAPIX on 'Ser-694', which results in the enhancement of ARHGEF7 activity and activation of RAC1. Promotes neuronal differentiation and neurite outgrowth by activation and phosphorylation of MARK2 on 'Ser-91', 'Ser-92', 'Ser-93' and 'Ser-294'. Promotes nuclear export of HDAC5 and binding to 14-3-3 by phosphorylation of 'Ser-259' and 'Ser-498' in the regulation of muscle cell differentiation. Regulates NUMB-mediated endocytosis by phosphorylation of NUMB on 'Ser-276' and 'Ser-295'. Involved in the regulation of basal and estrogen-stimulated migration of medulloblastoma cells through ARHGEF7/BETAPIX phosphorylation (By similarity). Is required for proper activation of cyclin-D1/CDK4 complex during G1 progression in diploid fibroblasts. Plays a role in K(+) and ANG2-mediated regulation of the aldosterone synthase (CYP11B2) to produce aldosterone in the adrenal cortex. Phosphorylates EIF4G3/eIF4GII. In vitro phosphorylates CREB1, ATF1, CFTR, MYL9 and SYN1/synapsin I.^{[1] [2] [3] [4] [5] [6] [7] [8]}

See Also

• Calcium/calmodulin dependent protein kinase 3D structures

References

1. ↑ McKinsey TA, Zhang CL, Olson EN. Activation of the myocyte enhancer factor-2 transcription factor by calcium/calmodulin-dependent protein kinase-stimulated binding of 14-3-3 to histone deacetylase 5. Proc Natl Acad Sci U S A. 2000 Dec 19;97(26):14400-5. PMID:11114197 doi:http://dx.doi.org/10.1073/pnas.260501497
2. ↑ Condon JC, Pezzi V, Drummond BM, Yin S, Rainey WE. Calmodulin-dependent kinase I regulates adrenal cell expression of aldosterone synthase. Endocrinology. 2002 Sep;143(9):3651-7. PMID:12193581 doi:http://dx.doi.org/10.1210/en.2001-211359
3. ↑ Qin H, Raught B, Sonenberg N, Goldstein EG, Edelman AM. Phosphorylation screening identifies translational initiation factor 4GII as an intracellular target of Ca(2+)/calmodulin-dependent protein kinase I. J Biol Chem. 2003 Dec 5;278(49):48570-9. Epub 2003 Sep 24. PMID:14507913 doi:http://dx.doi.org/10.1074/jbc.M308781200
4. ↑ Kahl CR, Means AR. Regulation of cyclin D1/Cdk4 complexes by calcium/calmodulin-dependent protein kinase I. J Biol Chem. 2004 Apr 9;279(15):15411-9. Epub 2004 Jan 30. PMID:14754892 doi:http://dx.doi.org/10.1074/jbc.M312543200
5. ↑ Kamata A, Sakagami H, Tokumitsu H, Owada Y, Fukunaga K, Kondo H. Spatiotemporal expression of four isoforms of Ca2+/calmodulin-dependent protein kinase I in brain and its possible roles in hippocampal dendritic growth. Neurosci Res. 2007 Jan;57(1):86-97. Epub 2006 Oct 23. PMID:17056143 doi:http://dx.doi.org/10.1016/j.neures.2006.09.013
6. ↑ Uboha NV, Flajolet M, Nairn AC, Picciotto MR. A calcium- and calmodulin-dependent kinase Ialpha/microtubule affinity regulating kinase 2 signaling cascade mediates calcium-dependent neurite outgrowth. J Neurosci. 2007 Apr 18;27(16):4413-23. PMID:17442826 doi:http://dx.doi.org/10.1523/JNEUROSCI.0725-07.2007
7. ↑ Saneyoshi T, Wayman G, Fortin D, Davare M, Hoshi N, Nozaki N, Natsume T, Soderling TR. Activity-dependent synaptogenesis: regulation by a CaM-kinase kinase/CaM-kinase I/betaPIX signaling complex. Neuron. 2008 Jan 10;57(1):94-107. doi: 10.1016/j.neuron.2007.11.016. PMID:18184567 doi:http://dx.doi.org/10.1016/j.neuron.2007.11.016
8. ↑ Neal AP, Molina-Campos E, Marrero-Rosado B, Bradford AB, Fox SM, Kovalova N, Hannon HE. CaMKK-CaMKI signaling pathways differentially control axon and dendrite elongation in cortical neurons. J Neurosci. 2010 Feb 24;30(8):2807-9. doi: 10.1523/JNEUROSCI.5984-09.2010. PMID:20181577 doi:http://dx.doi.org/10.1523/JNEUROSCI.5984-09.2010