title: STRIPAK complexes: structure, biological function, and involvement in human diseases.
abstract: The mammalian striatin family consists of three proteins, striatin, S/G2 nuclear autoantigen, and zinedin. Striatin family members have no intrinsic catalytic activity, but rather function as scaffolding proteins. Remarkably, they organize multiple diverse, large signaling complexes that participate in a variety of cellular processes. Moreover, they appear to be regulatory/targeting subunits for the major eukaryotic serine/threonine protein phosphatase 2A. In addition, striatin family members associate with germinal center kinase III kinases as well as other novel components, earning these assemblies the name striatin-interacting phosphatase and kinase (STRIPAK) complexes. Recently, there has been a great increase in functional and mechanistic studies aimed at identifying and understanding the roles of STRIPAK and STRIPAK-like complexes in cellular processes of multiple organisms. These studies have identified novel STRIPAK and STRIPAK-like complexes and have explored their roles in specific signaling pathways. Together, the results of these studies have sparked increased interest in striatin family complexes because they have revealed roles in signaling, cell cycle control, apoptosis, vesicular trafficking, Golgi assembly, cell polarity, cell migration, neural and vascular development, and cardiac function. Moreover, STRIPAK complexes have been connected to clinical conditions, including cardiac disease, diabetes, autism, and cerebral cavernous malformation. In this review, we discuss the expression, localization, and protein domain structure of striatin family members. Then we consider the diverse complexes these proteins and their homologs form in various organisms, emphasizing what is known regarding function and regulation. Finally, we explore possible roles of striatin family complexes in disease, especially cerebral cavernous malformation.
authors: Department of Biochemistry and Winship Cancer Institute, and Biochemistry, Cell, Developmental Biology Graduate Program, Emory University School of Medicine, 1510 Clifton Road, Atlanta, GA 30322, USA. Electronic address: jhwang8231@gmail.com.
authors: Juyeon
authors: J
authors: Hwang
authors: Department of Biochemistry and Winship Cancer Institute, and Biochemistry, Cell, Developmental Biology Graduate Program, Emory University School of Medicine, 1510 Clifton Road, Atlanta, GA 30322, USA. Electronic address: dpallas@emory.edu.
authors: David C
authors: DC
authors: Pallas
mesh_terms: D002148:Calmodulin-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D002148:Calmodulin-Binding Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C491925:STRN protein, human
keywords: 8p11 myeloproliferative syndrome; AJ; APC; ARD; ARVC; Basket; Bsk; CCM; CCM patient endothelial cells; CCM-ECs; CCT/TRiC; CTTNBP2/NL; CaM; Cav-1; Ccm3; Cka; DCM; DUB; Disease; Drosophila Jun N-terminal kinase; Drosophila Mob3 functional homolog; Drosophila Ras association domain family protein; Drosophila extracellular signal-regulated kinase; EGFR; EMS; ERM; ERMES; ERα; Eps15; Erk; FAR; FAT; FGFR1OP2; GAIP-interacting protein, C terminus; GAP; GCKIII; GH; GIPC; GTPase activating protein; HBMECs; HEG1; HGNC; HMVECs; HUGO Gene Nomenclature Committee; HUVECs; Hemipterous; Hep; Hippo; Hpo; ICAP-1; IRF-3; Jra; Jun-related antigen; K-Rev interaction trapped 1; Kay; Krit1; MASK; MEKK3; MLC; MR; Map4k4; Mink1; Misshapen; Mob3; Msn; Msn-like kinase 1; Mst; Mst3 and Sok1-related kinase; N-methyl-d-aspartate; N-methyl-d-aspartate receptors; NDPK; NLS; NMDA; NMDARs; OSM; PDCD10; PDGFRA; PP2A; PPARγ; PTB; PTP; ROCK; RTKs; Rho-associated coiled coil-forming kinase; RhoA; S/G(2) nuclear autoantigen; SG2NA; SIKE; SIN; SIN-inhibitory PP2A complex; SIP; SLMAP; SPB; SR; STRIP1/2; STRIPAK; Sok1; Striatin; TF-1 cell apoptosis related gene-15; TFAR15; TJ; TLR3; TORC1; TRAF2- and NCK-interacting kinase; Tnf-α; Tnik; Toll-like receptor 3; WD; Ysk1; adenomatous polyposis coli; adherens junction; armadillo repeat domain; arrhythmogenic right ventricular cardiomyopathy; calmodulin; caveolin-1; cerebral cavernous malformation 3; cerebral cavernous malformations; chaperonin containing TCP-1/TCP-1 ring complex; connector of kinase to AP-1; cortactin-binding protein 2/cortactin-binding protein 2, N-terminal-like; dErk; dJnk; dMob4; dRassf; deubiquitinase; dilated cardiomyopathy; eNOS; endoplasmic reticulum–mitochondria encounter structure; endothelial nitric oxide synthase; epidermal growth factor receptor; epidermal growth factor receptor substrate 15; estrogen receptor alpha; extracellular signal-regulated kinase; ezrin/radixin/moesin; factor arrest; fibroblast growth factor receptor 1 oncogene partner 2; focal adhesion targeting; germinal center kinase III; glycine–histidine; heart of glass 1; human brain microvascular endothelial cells; human dermal microvascular endothelial cells; human umbilical vein endothelial cells; integrin cytoplasmic associated protein-1; interferon regulatory factor 3; kayak; mDia; mammalian homolog of Drosophila diaphanous; mammalian sterile 20-like; mineralocorticoid receptor; mitogen-activated protein kinase kinase kinase 3; mitogen-activated protein kinase kinase kinase kinase 4; monopolar spindle-one-binder family 3; myosin light chain; nuclear localization signal; nucleoside-diphosphate kinase; osmosensing scaffold for MEKK3; peroxisome proliferator-activated receptor γ; phosphotyrosine-binding; platelet derived growth factor receptor alpha; programmed cell death 10; protein phosphatase 2A; protein-tyrosine phosphatase; ras homolog gene family member A; receptor tyrosine kinases; sarcolemmal membrane-associated protein; sarcoplasmic reticulum; septation initiation network; spindle pole body; sterile 20/oxidant stress-response kinase 1; striatin interacting proteins 1 and 2; striatin-interacting phosphatase and kinase; suppressor of IKKɛ; target of rapamycin complex 1; tight junction; tryptophan–aspartate; tumor necrosis factor alpha; yeast Sps1/sterile-20-related kinase 1