Calmodulin as a protein linker and a regulator of adaptor/scaffold proteins

Article ID	Journal	Published Year	Pages	File Type
8303705	Biochimica et Biophysica Acta (BBA) - Molecular Cell Research	2018	38 Pages	PDF

Abstract

Calmodulin (CaM) is a universal regulator for a huge number of proteins in all eukaryotic cells. Best known is its function as a calcium-dependent modulator of the activity of enzymes, such as protein kinases and phosphatases, as well as other signaling proteins including membrane receptors, channels and structural proteins. However, less well known is the fact that CaM can also function as a Ca2Â +-dependent adaptor protein, either by bridging between different domains of the same protein or by linking two identical or different target proteins together. These activities are possible due to the fact that CaM contains two independently-folded Ca2Â + binding lobes that are able to interact differentially and to some degree separately with targets proteins. In addition, CaM can interact with and regulates several proteins that function exclusively as adaptors. This review provides an overview over our present knowledge concerning the structural and functional aspects of the role of CaM as an adaptor protein and as a regulator of known adaptor/scaffold proteins.

Keywords

EGFR NF-κB PI3K TRPA1 TRPV1 IGF Jnk NFAT TNC MBP EGTA HRP GAD PP2A pKa SHC NMDA N-methyl-d-aspartate GPCR p75NTR PKC MAP-2 ERα FADD STIM1 SOS SPB PTB TNFR IQGAP1 GEF EPS15 Jun N-terminal kinase SH2 TRADD BCL10 LRP4 MLCK DR6 death receptor 6 SH3 NDPK NHE1 Orai1 Sex-determining Region on the Y Chromosome PDB id CARMA1 W-7 ALG-2 CaM-binding protein epidermal growth factor receptor substrate 15 Trans-activator of transcription W-13 N-(4-aminobutyl)-5-chloro-2-naphthalenesulfonamide CaM-BD Munc13-1 CaM-binding domain nuclear magnetic resonance MAPK N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide TnI adenylyl cyclase Alix EDTA ethylene glycol-bis(2-aminoethylether)-N,N,N′,N′-tetraacetic acid Ethylenediaminetetraacetic acid TAT Troponin C Troponin I Troponin T NMR Protein-protein interaction TnT Src homology domain 2 Src homology domain 3 caspase-recruitment domain Nucleoside diphosphate kinase CAM Sry Nuclear Factor of Activated T Cells guanine nucleotide exchange factor Insulin-like growth factor nuclear factor κB Phosphatidylinositol 3-kinase Stromal interaction molecule 1 Mint pleckstrin-homology HIV-1 human immunodeficiency virus 1 transient receptor potential ankyrin 1 Transient receptor potential vanilloid 1 Horseradish peroxidase Adaptor proteins protein phosphatase 2A Fas-associated protein with death domain microtubule-associated protein 2 Low-density lipoprotein receptor-related protein 4 Scaffold proteins protein kinase A Protein kinase C mitogen-activated protein kinase son of sevenless CARD Calmodulin Myosin light-chain kinase Glutamate decarboxylase Estrogen receptor α Epidermal growth factor receptor tumor necrosis factor receptor Neurotrophin receptor G protein-coupled receptor