Main Article Content
A precise cellular response to both internal and external stimuli is crucial for the normal growth and development of all organisms. Almost all such responses are now known to be carried out by signal transduction pathways that involve signaling molecules such as receptors, second messengers, modifiers, effectors such as kinases, transcription factors, etc. Of critical importance are the modifiers such as scaffold proteins that impart spatial and temporal regulatory features to the response. A-Kinase Anchoring Proteins (AKAPs) are one such well-studied scaffold proteins that bind to cAMP-dependent protein kinase (PKA) and an array of signaling proteins. AKAPs are known to amplify, accelerate, localize and bring about specificity to the response. The AKAP-PKA complex is well studied and it has been found that regulatory subunits of PKA bind to the amphipathic helix of the AKAPs via their dimerization and docking (D/D) domains with what is commonly referred to as the RII-fold. This domain and fold is a characteristic feature of all the known regulatory subunits of PKA. However, recently, some molecules with an RII-fold have become known to bind to the amphipathic helices of AKAPs via their D/D-like domains; among others, these include several sperm proteins such as ropporin, AKAP-associated sperm protein (ASP), Sperm Protein-17 (SP-17) and fibrosheathin II (FSII) and others like DPY-30, RSP9, RSP11 and Myc-Binding Protein-1. The list of these types of proteins is growing and is referred to here as the atypical RII proteins (R2D2 proteins).
Authors will be required to fill out the below copyright transfer form during the peer-review process and attach it along with their submission. In return, Knowledge Enterprises Journals grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by Knowledge Enterprises Journals.
2. Ali A, Tyagi S. (2017) Diverse roles of WDR5-RbBP5-ASH2L-DPY30 (WRAD) complex in the functions of the SET1 histone methyltransferase family. J. Biosci; 42: 155–159.
3. Angelo R, Rubin CS. (1998) Molecular characterization of an Anchor Protein (AKAPCE) that binds the RI subunit (RCE) of type I Protein Kinase A from Caenorhabditis elegans. J. Biol. Chem; 273: 14633–14643.
4. Beebe S. J. and Corbin J. D. (1986) Cyclic Nucleotide-Dependent Protein Kinases, in The Enzymes: Control by Phosphorylation Part A, eds Boyer P. D., Krebs E. G. (Academic Press, New York), 17:43–111.
5. Brostrom CO, Corbin JD, King CA, Krebs EG. (1971) Interaction of the subunits of adenosine 3′:5′-cyclic monophosphate-dependent protein kinase of muscle. Proc Natl Acad Sci USA; 68: 2444–2447.
6. Carnegie GK, Means CK, Scott JD. A-kinase anchoring proteins: from protein complexes to physiology and disease. IUBMB Life. 2009; 61:394-406.
7. Carr DW, Hausken ZE, Fraser ID, Stofko-Hahn RE, Scott JD. (1992) Association of the type II cAMP-dependent protein kinase with a human thyroid RII-anchoring protein. Cloning and characterization of the RII-binding domain. J. Biol. Chem. 267:13376–13382.
8. Carr DW, Fujita A, Stentz CL, Liberty GA, Olson GE, Narumiya S. (2001) Identification of Sperm-specific Proteins That Interact with A-kinase Anchoring Proteins in a Manner Similar to the Type II Regulatory Subunit of PKA. J Biol Chem; 276: 17332-17338.
9. Carrera A, Gerton GL, Moss SB. (1994) The major fibrous sheath polypeptide of mouse sperm: structural and functional similarities to the A-kinase anchoring proteins. Dev. Biol; 165: 272–284.
10. Calejo AI, Taskén K. (2015) Targeting protein-protein interactions in complexes organized by A kinase anchoring proteins. Front Pharmacol; 6: 192.
11. Clegg CH, Cadd GG, McKnight GS. (1988) Genetic characterization of a brain-specific form of the type I regulatory subunit of cAMP-dependent protein kinase. Proc. Natl. Acad. Sci. USA; 85: 3703–3707.
12. Coghlan VM, Perrino BA, Howard M, Langeberg LK, Hicks JB, Gallatin WM, Scott JD. (1995) Association of protein kinase A and protein phosphatase 2B with a common anchoring protein, Science; 267: 108–111.
13. Cummings DE, Brandon EP, Planas JV, Motamed K, Idzerda RL, McKnight GS. (1996) Genetically lean mice result from targeted disruption of the RIIbeta subunit of protein kinase A. Nature; 382: 622–626.
14. Dharmarajan V, Lee JH, Patel A, Skalnik DG and Cosgrove MS. (2012) Structural basis for WDR5 interaction (Win) motif recognition in human SET1 family histone methyltransferases. J. Biol. Chem; 287: 27275–27289.
15. Dou Y, Milne TA, Ruthenburg AJ, Lee S, Lee JW, Verdine GL, Allis CD and Roeder RG. (2006) Regulation of MLL1 H3K4 methyltransferase activity by its core components. Nat. Struct. Mol. Biol; 13: 713–719.
16. Erlichman J, Rosenfeld R, Rosen OM. (1974) Phosphorylation of a Cyclic Adenosine 3' : 5'-Monophosphate-dependent Protein Kinase from Bovine Cardiac Muscle. J. Biol. Chem; 249: 5000–5003.
17. Ernst P, Vakoc CR. (2012) WRAD: enabler of the SET1-family of H3K4 methyltransferases. Brief. Funct. Genomics. 11 217–226.
18. Erlichman J, Gutierrez-Juarez R, Zucker S, Mei X, Orr GA. (1999) Developmental expression of the protein kinase C substrate/binding protein (clone 72/SSeCKS) in rat testis. Eur. J. Biochem; 263: 797–805.
19. Fisher EH, Krebs EG. (1955) Conversion of phosphorylase b to phosphorylase a in muscle extracts. J Biol Chem; 216: 121-32.
20. Fiedler SE, Bajpai M and Carr DW. (2008) Identification and characterization of RHOA-interacting proteins in bovine spermatozoa. Biol Reprod; 78: 184-192.
21. Fiedler SE, Dudiki T, Vijayaraghavan S, Carr DW. (2013) Loss of R2D2 proteins ROPN1 and ROPN1L causes defects in murine sperm motility, phosphorylation, and fibrous sheath integrity. Biol Reprod; 88(2): 41.
22. Fujita A, Nakamura K, Kato T, Watanabe N, Ishizaki T, Kimura K, Mizoguchi A and Narumiya S. (2000) Ropporin, a sperm-specific binding protein of rhophilin, that is localized in the fibrous sheath of sperm flagella. Journal of Cell Science 113, 103-112.
23. Furusawa M, Onishi T, Taira T, Iguchi-Ariga SM, Ariga H. (2000) AMY-1 is a trigger for the erythrocyte differentiation of K562 cells. Int J Oncol; 16: 339–45.
24. Furusawa M, Taira T, Iguchi-Ariga SM, Ariga H. (2002) AMY-1 interacts with SAKAP84 and AKAP95 in the cytoplasm and the nucleus, respectively, and inhibits cAMP-dependent protein kinase activity by preventing binding of its catalytic subunit to A-kinase-anchoring protein (AKAP) complex. J Biol Chem; 277: 50885–92.
25. Furusawa M, Ohnishi T, Taira T, Iguchi-Ariga SM, Ariga H. (2001) AMY-1, a c-Myc binding protein, is localized in the mitochondria of sperm by association with S-AKAP84, an anchor protein of cAMP-dependent protein kinase. J Biol Chem; 276: 36647–51.
26. Gill GN, Garren LD. (1970) A cyclic-3′,5′-adenosine monophosphate dependent protein kinase from the adrenal cortex: comparison with a cyclic AMP binding protein. Biochem Biophys Res Commun; 39: 335–343.
27. Gopal R, Foster KW, Yang P. (2012) The DPY-30 domain and its flanking sequence mediate the assembly and modulation of flagellar radial spoke complexes. Mol Cell Biol; 32: 4012-24.
28. Han B, Poppinga WJ, Schmidt M. (2015) Scaffolding during the cell cycle by A-kinase anchoring proteins. Pflugers Arch. 467(12):2401-11.
29. Hofmann F, Beavo JA, Bechtel PJ, Krebs EG. (1975) Comparison of adenosine 3':5'-monophosphate-dependent protein kinases from rabbit skeletal and bovine heart muscle. J. Biol. Chem. 250: 7795–7801.
30. Horowitz JA, Wasco W, Leiser M, Orr GA. (1988) Interaction of the regulatory subunit of a type II cAMP-dependent protein kinase with mammalian sperm flagellum. J. Biol. Chem. 263: 2098–2104.
31. Huang LJS, Durick K, Weiner JA, Chun J, Taylor SS. (1997a) Identification of a Novel Protein Kinase A Anchoring Protein that binds both Type I and Type II Regulatory Subunits, J. Biol. Chem. 272: 8057–8064.
32. Huang LJS, Durick K, Weiner JA, Chun J, Taylor SS. (1997b) D-AKAP2, a novel protein kinase A anchoring protein with a putative RGS domain. Proc. Natl. Acad. Sci. USA; 94: 11184–11189.
33. Hsu DR, Chuang PT, Meyer BJ. (1995) DPY-30, a nuclear protein essential early in embryogenesis for Caenorhabditis elegans dosage compensation.Development 121: 3323–3334.
34. Huang B, Piperno G, Ramanis Z, Luck DJ. (1981) Radial spokes of Chlamydomonas flagella: genetic analysis of assembly and function. J Cell Biol; 88:80–88.
35. Ishizaki R, Shin HW, Iguchi-Ariga SM, Ariga H, Nakayama K. (2006) AMY-1 (associate of Myc-1) localization to the trans-Golgi network through interacting with BIG2, a guanine-nucleotide exchange factor for ADP-ribosylation factors. Genes Cells; 11: 949–59.
36. Jahnsen J, Hedin L, Kidd VJ, Beattie WG, Lohmann SM, Walter V, Durica J, Schultz TZ, Schiltz E, Browner M, Lawrence CB, Goldman D, Ratoosh SL, Richards JS. (1986) Molecular cloning, cDNA structure, and regulation of the regulatory subunit of type II cAMP-dependent protein kinase from rat ovarian granulosa cells. J. Biol. Chem. 261:12352–12361.
37. Jiang H, Shukla A, Wang X, Chen WY, Bernstein BE, Roeder RG. (2011) Role for Dpy-30 in ES cell-fate specification by regulation of H3K4 methylation within bivalent domains. Cell; 144: 513-25.
38. Knighton DR, Zheng JH, Ten Eyck LF, Xuong NH, Taylor SS, Sowadski JM. (1991). Structure of a peptide inhibitor bound to the catalytic subunit of cyclic adenosine monophosphate-dependent protein kinase. Science; 253: 414–420.
39. Klauck TM, Faux MC, Labudda K, Langeberg LK, Jaken S, Scott JD. (1996) Coordination of Three Signaling Enzymes by AKAP79, a Mammalian Scaffold Protein Science; 271: 1589–1592.
40. Lee DC, Carmichael DF, Krebs EG, McKnight GS. (1983) Isolation of a cDNA clone for the type I regulatory subunit of bovine cAMP-dependent protein kinase. Proc. Natl. Acad. Sci. USA; 80: 3608–3612.
41. Lin RY, Moss SB, Rubin CS. (1995) Characterization of S-AKAP84, a Novel Developmentally Regulated A Kinase Anchor Protein of Male Germ Cells. J. Biol. Chem; 270: 27804.
42. Ma Y, Taylor SS. (2008) A Molecular Switch for Targeting between Endoplasmic Reticulum (ER) and Mitochondria. Conversion of a Mitochondria-targeting element into an ER-targeting signal in DAKAP1_S. (2008) J Biol Chem; 283: 11743–11751.
43. Manning G, Whyte DB, Martinez R, Hunter T, Sudarsanam S. (2002) The protein kinase complement of the human genome. Science; 298: 1912–1934.
44. Mei X, Singh IS, Erlichman J, Orr GA. (1997) Cloning and Characterization of a Testis‐Specific, Developmentally Regulated A‐Kinase‐Anchoring Protein (Takap‐80) Present on the Fibrous Sheath of Rat Sperm. Eur. J. Biochem; 246: 425–432.
45. Miki K, Eddy EM. (1999) Single Amino Acids Determine Specificity of Binding of Protein Kinase A Regulatory Subunits by Protein Kinase A Anchoring Proteins. J. Biol. Chem; 274: 29057–29062.
46. Nauert JB, Klauck TM, Langeberg LK, Scott JD. (1997) Gravin, an autoantigen recognized by serum from myasthenia gravis patients, is a kinase scaffold protein, Curr. Biol; 7: 52–62.
47. Naaby-Hansen S, Mandal A, Wolkowicz MJ, Sen B, Westbrook VA, Shetty J, Coonrod SA, Klotz KL, Kim YH, Bush LA, Flickinger CJ, Herr JC. (2002) CABYR, a novel calcium-binding tyrosine phosphorylation-regulated fibrous sheath protein involved in capacitation. Dev Biol; 242: 236–254.
48. Newell AE, Fiedler SE, Ruan JM, Pan PJ, Deininger WJ, Corless CL and Carr DW. (2008) Protein kinase A RII-like (R2D2) proteins exhibit differential localization and AKAP interaction. Cell Motil Cytoskeleton; 65: 539-552.
49. Pariset C, Weinman S. (1994) Differential localization of two isoforms of the regulatory subunit RIIα of cAMP‐dependent protein kinase in human sperm: biochemical and cytochemical study. Mol. Reprod. Dev; 39: 415–422.
50. Patel A, Vought VE, Dharmarajan V and Cosgrove MS. (2011) A novel non-SET domain multi-subunit methyltransferase required for sequential nucleosomal histone H3 methylation by the mixed lineage leukemia protein-1 (MLL1) core complex. J. Biol. Chem; 286: 3359–3369.
51. Rao VG, Sarafdar RB, Chowdhury TS, Sivadas P, Yang P, Dongre PM, D'Souza JS. (2016) Myc-binding protein orthologue interacts with AKAP240 in the central pair apparatus of the Chlamydomonas flagella. BMC Cell Biol; 17: 24.
52. Reinton N, Collas P, Haugen TB, Skalhegg BS, Hansson V, Jahnsen T, Tasken K. (2000) Localization of a novel human A-kinase-anchoring protein, hAKAP220, during spermatogenesis. Dev. Biol. 223:194–204.
53. Sarkar D, Erlichman J, Rubin CS. (1984) Identification of a calmodulin-binding protein that co-purifies with the regulatory subunit of brain protein kinase II. J. Biol. Chem; 259: 9840–9846.
54. Satouh Y, Inaba K. (2009) Proteomic characterization of sperm radial spokes identifies a novel spoke protein with an ubiquitin domain. FEBS Lett. 583(13): 2201–2207.
55. Schillace RV, Scott JD. (1999) Association of the type 1 protein phosphatase PP1 with the A-kinase anchoring protein AKAP220. Curr. Biol; 9: 321–324.
56. Schmidt PH, Dransfield DT, Claudio JO, Hawley RG, Trotter KW, Milgram SL, Goldenring JR (1999) AKAP350, a multiply spliced protein kinase A-anchoring protein associated with centrosomes. J Biol Chem. 1999 Jan 29; 274(5):3055-66.
57. Scott JD, Glaccum MB, Zoller MJ, Uhler MD, Helfman DM, McKnight GS, Krebs EG. (1987) The molecular cloning of a type II regulatory subunit of the cAMP-dependent protein kinase from rat skeletal muscle and mouse brain. Proc. Natl. Acad. Sci. USA; 84: 5192–5196.
58. Sen B, Mandal A, Wolkowicz MJ, Kim YH, Reddi PP, Shetty J, Bush LA, Flickinger CJ, Herr JC. (2003) Splicing in murine CABYR and its genomic structure, Gene; 22: 310:67-78.
59. Shanks RA, Steadman BT, Schmidt PH, Goldenring JR. (2002a) AKAP350 at the Golgi Apparatus I. Identification of a distinct Golgi apparatus targeting motif in AKAP350. J Biol. Chem; 277, 40967-40972.
60. Shanks RA, Larocca MC, Berryman M, Edwards JC, Urushidani T, Navarre J, Goldenring JR. (2002b) AKAP350 at the Golgi apparatus. II. Association of AKAP350 with a novel chloride intracellular channel (CLIC) family member. J Biol Chem; 277: 40973-80.
61. Shinsky SA, Cosgrove MS. (2015) Unique role of the WD-40 repeat protein 5 (WDR5) subunit within the mixed lineage leukemia 3 (MLL3) histone methyltransferase complex. J. Biol. Chem; 290: 25819–25833.
62. Sim AT, Scott JD. (1999) Targeting of PKA, PKC and protein phosphatases to cellular microdomains. Cell Calcium; 26: 209-217.
63. Steward MM, Lee J, O’Donovan A, Wyatt M, Bernstein BE, Shilatifard A, Donovan AO, Wyatt M, et al. (2006) Molecular regulation of H3K4 trimethylation by ASH2L, a shared subunit of MLL complexes. Nat. Struct. Mol. Biol. 13: 852–854.
64. Stolc V, Samanta MP, Tongprasit W, Marshall WF. (2005) Genome-wide transcriptional analysis of flagellar regeneration in Chlamydomonas reinhardtii identifies orthologs of ciliary disease genes. Proc Natl Acad Sci USA; 102: 3703-7.
65. South PF, Fingerman IM, Mersman DP, Du H-N and Briggs SD. (2010) A Conserved Interaction between the SDI Domain of Bre2 and the Dpy-30 Domain of Sdc1 Is Required for Histone Methylation and Gene Expression, J Biol. Chem; 285: 595-607.
66. Sutherland EW, Rall TW. (1958) Fractionation and characterization of a cyclic adenine ribonucleotide formed by tissue particles. J Biol Chem; 232: 1077-91.
67. Taira T, Maeda J, Onishi T, Kitaura H, Yoshida S, Kato H, et al. (1998) AMY-1, a novel C-MYC binding protein that stimulates transcription activity of C-MYC. Genes Cells; 3: 549–65.
68. Tasken K, Aandahl EM. (2004) Localized effects of cAMP mediated by distinct routes of protein kinase A. Physiol Rev. 2004; 84:137-167.
69. Takahashi M, Shibata H, Shimakawa M, Miyamoto M, Mukai H, Ono Y. (1999) Characterization of a novel giant scaffolding protein, CG-NAP, that anchors multiple signaling enzymes to centrosome and the golgi apparatus. J Biol Chem; 274: 17267-74.
70. Takahashi M, Yamagiwa A, Nishimura T, Mukai H, Ono Y (2002) Centrosomal proteins CG-NAP and kendrin provide microtubule nucleation sites by anchoring gamma-tubulin ring complex. Mol Biol Cell; 13: 3235-45.
71. Tao M, Salas ML, Lipmann F. (1970) Mechanism of activation by adenosine 3′:5′-cyclic monophosphate of a protein phosphokinase from rabbit reticulocytes. Proc Natl Acad Sci USA; 67: 408–414.
72. Tremblay V, Zhang P, Chaturvedi C-P, Thornton J, Brunzelle JS, Skiniotis G, Shilatifard A, Brand M, Couture J-F. (2014) Molecular Basis for DPY-30 Association to COMPASS-like and NURF Complexes. Structure 22, 1821–1830.
73. Torres-Quesada O, Mayrhofer JE, Stefan E. (2017) The many faces of compartmentalized PKA signalosomes. Cell Signal; 37:1-11.
74. Vijayaraghavan S, Goueli SA, Davey MP, Carr DW. (1997) Protein Kinase A-anchoring Inhibitor Peptides Arrest Mammalian Sperm Motility. J. Biol. Chem. 272:4747–4752.
75. Vijayaraghavan S, Liberty GA, Mohan J, Winfrey VP, Olson GE, Carr DW. (1999) Isolation and molecular characterization of AKAP110, a novel, sperm-specific protein kinase A-anchoring protein. Mol. Endocrinol; 13:705–717.
76. Walsh DA, Perkins JP, Krebs EG. (1968) An adenosine 3',5'-monophosphate-dependant protein kinase from rabbit skeletal muscle. J Biol Chem; 243: 3763-5.
77. Wang X, Lou Z, Dong X, Yang W, Peng Y, Yin B, Gong Y, Yuan J, Zhou W, Bartlam M, Peng X, Rao Z. (2009) Crystal structure of the C-terminal domain of human DPY-30-like protein: A component of the histone methyltransferase complex. J Mol Biol; 390: 530-7.
78. Weber IT, Steitz TA, Bubis J, Taylor SS. (1987) Predicted structures of cAMP binding domains of type I and II regulatory subunits of cAMP-dependent protein kinase. Biochemistry; 26: 343–351.
79. Witczak O, Skålhegg BS, Keryer G, Bornens M, Taskén K, Jahnsen T, Orstavik S (1999) Cloning and characterization of a cDNA encoding an A-kinase anchoring protein located in the centrosome, AKAP450. EMBO J; 18: 1858-68.
80. Wong W, Scott JD. (2004) AKAP signalling complexes: focal points in space and time, Nature Reviews Molecular Cell Biology; 5: 959-970.
81. Xu Z, Gong Q, Xia B, Groves B, Zimmermann M, Mugler C, Mu D, Matsumoto B, et al. (2009) A role of histone H3 lysine 4 methyltransferase components in endosomal trafficking. J. Cell Biol. 186 343–353.
82. Yang P, Diener DR, Yang C, Kohno T, Pazour GJ, Dienes JM, Agrin NS, King SM, Sale WS, Kamiya R, Rosenbaum JL, and Witman GB. (2006) Radial spoke proteins of Chlamydomonas flagella. J Cell Sci; 119: 1165–1174.
83. Young SA, Miyata H, Satouh Y, Aitken RJ, Baker MA, Ikawa M. (2016) CABYR is essential for fibrous sheath integrity and progressive motility in mouse spermatozoa. J Cell Sci; 129: 4379-4387.
84. Yukitake H, Furusawa M, Taira T, Iguchi-Ariga SM, Ariga H. (2002a) AMAP-1, a novel testis-specific AMY-1-binding protein, is differentially expressed during the course of spermatogenesis. Biochim Biophys Acta; 1577: 126–32.
85. Yukitake H, Furusawa M, Taira T, Iguchi-Ariga SM, Ariga H. (2002b) AAT-1, a novel testis-specific AMY-1-binding protein, forms a quaternary complex with AMY-1, A-kinase anchor protein 84, and a regulatory subunit of cAMP-dependent protein kinase and is phosphorylated by its kinase. J Biol Chem; 277: 45480–92.
86. Zhu H, Klemic JF, Chang S, Bertone P, Casamayor A, Klemic KG, Smith D, Gerstein M, Reed MA, Snyder M. (2008) Analysis of yeast protein kinases using protein chips. Nature Genet; 26: 283–289.
87. Zhang Y, Mittal A, Reid J, Reich S, Gamblin SJ and Wilson JR. (2015) Evolving catalytic properties of the MLL family SET domain. Structure; 23: 1921–1933.