Gene Symbol: Kalirin
Description: kalirin, RhoGEF kinase
Alias: Duo, Hapip, Kalirin, kalirin, P-CIP10, PAM COOH-terminal interactor protein 10, cyclin B1, huntingtin-associated protein interacting protein (duo), huntingtin-associated protein-interacting protein, protein Duo, serine/threonine kinase with Dbl- and pleckstrin homology domain, serine/threonine-protein kinase with Dbl- and pleckstrin homology domain
Species: rat
Products:     Kalirin

Top Publications

  1. Johnson R, Penzes P, Eipper B, Mains R. Isoforms of kalirin, a neuronal Dbl family member, generated through use of different 5'- and 3'-ends along with an internal translational initiation site. J Biol Chem. 2000;275:19324-33 pubmed
    b>Kalirin is a neuron-specific GDP/GTP exchange factor for Rho subfamily GTP-binding proteins. The major Kalirin transcripts in adult rat brain were identified...
  2. Ma X, Huang J, Kim E, Zhu Q, Kuchel G, Mains R, et al. Kalirin-7, an important component of excitatory synapses, is regulated by estradiol in hippocampal neurons. Hippocampus. 2011;21:661-77 pubmed publisher
    ..b>Kalirin-7 (Kal7), the major isoform of Kalirin in the adult hippocampus, is a Rho GDP/GTP exchange factor localized to ..
  3. Jones K, Srivastava D, Allen J, Strachan R, Roth B, Penzes P. Rapid modulation of spine morphology by the 5-HT2A serotonin receptor through kalirin-7 signaling. Proc Natl Acad Sci U S A. 2009;106:19575-80 pubmed publisher
    ..PAK is a downstream target of the neuronal Rac guanine nucleotide exchange factor (RacGEF) kalirin-7 that is important for spine remodeling...
  4. Alam M, Caldwell B, Johnson R, Darlington D, Mains R, Eipper B. Novel proteins that interact with the COOH-terminal cytosolic routing determinants of an integral membrane peptide-processing enzyme. J Biol Chem. 1996;271:28636-40 pubmed
    ..P-CIP2 and P-CIP10 may be members of a family of cytosolic proteins involved in the routing of membrane proteins that function in the regulated secretory pathway. ..
  5. Cahill M, Xie Z, Day M, Photowala H, Barbolina M, Miller C, et al. Kalirin regulates cortical spine morphogenesis and disease-related behavioral phenotypes. Proc Natl Acad Sci U S A. 2009;106:13058-63 pubmed publisher
    ..b>Kalirin is a brain-specific guanine-nucleotide exchange factor (GEF) for Rac-like GTPases and is a key regulator of spine ..
  6. Ma X, Kiraly D, Gaier E, Wang Y, Kim E, Levine E, et al. Kalirin-7 is required for synaptic structure and function. J Neurosci. 2008;28:12368-82 pubmed publisher
    ..Rho GTPases activated by GDP/GTP exchange factors (GEFs) play key roles in the developing and adult nervous system. Kalirin-7 (Kal7), the predominant adult splice form of the multifunctional Kalirin RhoGEF, includes a PDZ [postsynaptic ..
  7. McPherson C, Eipper B, Mains R. Kalirin expression is regulated by multiple promoters. J Mol Neurosci. 2004;22:51-62 pubmed
    b>Kalirin is a multidomain guanine nucleotide exchange factor for small GTPbinding proteins of the Rho family...
  8. Schiller M, Ferraro F, Wang Y, Ma X, McPherson C, Sobota J, et al. Autonomous functions for the Sec14p/spectrin-repeat region of Kalirin. Exp Cell Res. 2008;314:2674-91 pubmed publisher
    b>Kalirin is a GDP/GTP exchange factor (GEF) for Rho proteins that modulates the actin cytoskeleton in neurons...
  9. Chakrabarti K, Lin R, Schiller N, Wang Y, Koubi D, Fan Y, et al. Critical role for Kalirin in nerve growth factor signaling through TrkA. Mol Cell Biol. 2005;25:5106-18 pubmed
    b>Kalirin is a multidomain guanine nucleotide exchange factor (GEF) that activates Rho proteins, inducing cytoskeletal rearrangement in neurons...

More Information


  1. Xie Z, Srivastava D, Photowala H, Kai L, Cahill M, Woolfrey K, et al. Kalirin-7 controls activity-dependent structural and functional plasticity of dendritic spines. Neuron. 2007;56:640-56 pubmed
    ..in pyramidal neurons causes CaMKII-dependent phosphorylation of the guanine-nucleotide exchange factor (GEF) kalirin-7 at residue threonine 95, regulating its GEF activity, leading to activation of small GTPase Rac1 and rapid ..
  2. Ma X, Huang J, Wang Y, Eipper B, Mains R. Kalirin, a multifunctional Rho guanine nucleotide exchange factor, is necessary for maintenance of hippocampal pyramidal neuron dendrites and dendritic spines. J Neurosci. 2003;23:10593-603 pubmed
    ..b>Kalirin, a dual Rho GDP-GTP exchange factor, causes spine formation when overexpressed...
  3. Hayashi Takagi A, Takaki M, Graziane N, Seshadri S, Murdoch H, Dunlop A, et al. Disrupted-in-Schizophrenia 1 (DISC1) regulates spines of the glutamate synapse via Rac1. Nat Neurosci. 2010;13:327-32 pubmed publisher
    ..We found that DISC1 anchored Kalirin-7 (Kal-7), regulating access of Kal-7 to Rac1 and controlling the duration and intensity of Rac1 activation in ..
  4. Mandela P, Yankova M, Conti L, Ma X, Grady J, Eipper B, et al. Kalrn plays key roles within and outside of the nervous system. BMC Neurosci. 2012;13:136 pubmed publisher
    ..Examination of existing Kalrn knockout mouse models has focused only on neuronal phenotypes. However, Kalirin was first identified through its interaction with an enzyme involved in the synthesis and secretion of multiple ..
  5. Schiller M, Chakrabarti K, King G, Schiller N, Eipper B, Maciejewski M. Regulation of RhoGEF activity by intramolecular and intermolecular SH3 domain interactions. J Biol Chem. 2006;281:18774-86 pubmed
    ..The structure of the N-terminal SH3 domain of Kalirin was solved using NMR spectroscopy, and it folds much like other SH3 domains...
  6. Wang X, Cahill M, Werner C, Christoffel D, Golden S, Xie Z, et al. Kalirin-7 mediates cocaine-induced AMPA receptor and spine plasticity, enabling incentive sensitization. J Neurosci. 2013;33:11012-22 pubmed publisher
    ..what is their functional significance? We tested the hypothesis that the guanine-nucleotide exchange factor Kalirin-7 (Kal-7) couples cocaine-induced AMPAR and spine upregulation and that these adaptations underlie sensitization ..
  7. Jones K, Eng A, Raval P, Srivastava D, Penzes P. Scaffold protein X11α interacts with kalirin-7 in dendrites and recruits it to Golgi outposts. J Biol Chem. 2014;289:35517-29 pubmed publisher
    ..Dendritic spine structure is important for brain development and plasticity. Kalirin-7 is a guanine nucleotide-exchange factor for the small GTPase Rac1 and is a critical regulator of dendritic ..
  8. Penzes P, Beeser A, Chernoff J, Schiller M, Eipper B, Mains R, et al. Rapid induction of dendritic spine morphogenesis by trans-synaptic ephrinB-EphB receptor activation of the Rho-GEF kalirin. Neuron. 2003;37:263-74 pubmed
    ..Activation of the EphB receptor induces translocation of the Rho-GEF kalirin to synapses and activation of Rac1 and its effector PAK...
  9. Peng H, Chen G, Lai C, Hsieh M, Lin T. Spinal serum-inducible and glucocorticoid-inducible kinase 1 mediates neuropathic pain via kalirin and downstream PSD-95-dependent NR2B phosphorylation in rats. J Neurosci. 2013;33:5227-40 pubmed publisher
    ..Increasing evidence reveals that kalirin, a Rho-guanine nucleotide exchange factor, modulates PSD-95-NR2B-dependent neuroplasticity...
  10. Wu J, Fanaroff A, Sharma K, Smith L, Brian L, Eipper B, et al. Kalirin promotes neointimal hyperplasia by activating Rac in smooth muscle cells. Arterioscler Thromb Vasc Biol. 2013;33:702-8 pubmed publisher
    b>Kalirin is a multifunctional protein that contains 2 guanine nucleotide exchange factor domains for the GTPases Rac1 and RhoA...
  11. Harrington A, Li Q, Tep C, Park J, He Z, Yoon S. The role of Kalirin9 in p75/nogo receptor-mediated RhoA activation in cerebellar granule neurons. J Biol Chem. 2008;283:24690-7 pubmed publisher
    ..These results reveal a mechanism by which the fifth helix of p75 regulates RhoA activation. ..
  12. Penzes P, Johnson R, Alam M, Kambampati V, Mains R, Eipper B. An isoform of kalirin, a brain-specific GDP/GTP exchange factor, is enriched in the postsynaptic density fraction. J Biol Chem. 2000;275:6395-403 pubmed
    ..b>Kalirin is a brain-specific protein, first identified through its interaction with peptidylglycine-alpha-amidating ..
  13. Cahill M, Remmers C, Jones K, Xie Z, Sweet R, Penzes P. Neuregulin1 signaling promotes dendritic spine growth through kalirin. J Neurochem. 2013;126:625-35 pubmed publisher
    ..The effects of NRG1 and erbB4 on spines were mediated by the RacGEF kalirin, a well-characterized regulator of dendritic spines...
  14. Mains R, Alam M, Johnson R, Darlington D, Back N, Hand T, et al. Kalirin, a multifunctional PAM COOH-terminal domain interactor protein, affects cytoskeletal organization and ACTH secretion from AtT-20 cells. J Biol Chem. 1999;274:2929-37 pubmed
    ..b>Kalirin, a PAM cytosolic domain interactor protein with spectrin-like repeats and GDP/GTP exchange factor activity for ..
  15. Vishwanatha K, Wang Y, Keutmann H, Mains R, Eipper B. Structural organization of the nine spectrin repeats of Kalirin. Biochemistry. 2012;51:5663-73 pubmed
    ..We expressed and purified fragments of Kalirin containing from one to five putative SRs to determine whether they formed nested structures that could endow ..
  16. Alam M, Johnson R, Darlington D, Hand T, Mains R, Eipper B. Kalirin, a cytosolic protein with spectrin-like and GDP/GTP exchange factor-like domains that interacts with peptidylglycine alpha-amidating monooxygenase, an integral membrane peptide-processing enzyme. J Biol Chem. 1997;272:12667-75 pubmed
    ..P-CIP10 (kalirin), a member of the Dbl family of proteins, may serve as part of a signal transduction system linking the catalytic ..
  17. Nicholson D, Cahill M, Tulisiak C, Geinisman Y, Penzes P. Spatially restricted actin-regulatory signaling contributes to synapse morphology. J Neurochem. 2012;121:852-60 pubmed publisher
    ..Here we examine how the localization of the RacGEF kalirin-7, a well-characterized regulator of actin in spines, varies as a function of post-synaptic density area and ..
  18. Xin X, Wang Y, Ma X, Rompolas P, Keutmann H, Mains R, et al. Regulation of Kalirin by Cdk5. J Cell Sci. 2008;121:2601-11 pubmed publisher
    b>Kalirin, one of the few Rho guanine nucleotide exchange factors (GEFs) that contains spectrin-like repeats, plays a critical role in axon extension and maintenance of dendritic spines...
  19. Yan Y, Eipper B, Mains R. Kalirin-9 and Kalirin-12 Play Essential Roles in Dendritic Outgrowth and Branching. Cereb Cortex. 2015;25:3487-501 pubmed publisher
    ..The roles of endogenous Kalirin-9 (Kal9) and Kalirin-12 (Kal12), the Kalrn isoforms expressed before synaptogenesis, have not been studied in ..
  20. Lu J, Luo C, Bali K, Xie R, Mains R, Eipper B, et al. A role for Kalirin-7 in nociceptive sensitization via activity-dependent modulation of spinal synapses. Nat Commun. 2015;6:6820 pubmed publisher
    ..b>Kalirin-7 is a multifunctional guanine-nucleotide-exchange factor (GEF) for Rho GTPases that is characterized by its ..
  21. Penzes P, Johnson R, Sattler R, Zhang X, Huganir R, Kambampati V, et al. The neuronal Rho-GEF Kalirin-7 interacts with PDZ domain-containing proteins and regulates dendritic morphogenesis. Neuron. 2001;29:229-42 pubmed
    Spine function requires precise control of the actin cytoskeleton. Kalirin-7, a GDP/GTP exchange factor for Rac1, interacts with PDZ proteins such as PSD-95, colocalizing with PSD-95 at synapses of cultured hippocampal neurons...
  22. Miller M, Yan Y, Machida K, Kiraly D, Levy A, Wu Y, et al. Brain Region and Isoform-Specific Phosphorylation Alters Kalirin SH2 Domain Interaction Sites and Calpain Sensitivity. ACS Chem Neurosci. 2017;8:1554-1569 pubmed publisher
    ..Evaluation of the functional significance of multisite phosphorylation in a complex protein like Kalirin is difficult...
  23. Kiraly D, Lemtiri Chlieh F, Levine E, Mains R, Eipper B. Kalirin binds the NR2B subunit of the NMDA receptor, altering its synaptic localization and function. J Neurosci. 2011;31:12554-65 pubmed publisher
    ..b>Kalirin-7 (Kal7), a Rho guanine nucleotide exchange factor localized to the postsynaptic density (PSD), modulates ..
  24. Xu C, Ma X, Chen H, Zhou M, Qiao H, An S. Orbitofrontal cortex 5-HT2A receptor mediates chronic stress-induced depressive-like behaviors and alterations of spine density and Kalirin7. Neuropharmacology. 2016;109:7-17 pubmed publisher
    ..b>Kalirin-7 (Kal7) is an essential component of mature excitatory synapses for maintaining dendritic spines density, size ..
  25. Lee H, Lee J, Lee Y, Kim S, Park S, Kim H. Kalirin, a GEF for Rac1, plays an important role in FSTL-1-mediated glucose uptake in skeletal muscle cells. Cell Signal. 2017;29:150-157 pubmed publisher
    ..PAK1 knockdown or inhibition of Rac1 blocked FSTL-1-induced glucose uptake; moreover, kalirin, a Rac1 guanine nucleotide exchange factor (GEF), was induced by FSTL-1...
  26. May V, Schiller M, Eipper B, Mains R. Kalirin Dbl-homology guanine nucleotide exchange factor 1 domain initiates new axon outgrowths via RhoG-mediated mechanisms. J Neurosci. 2002;22:6980-90 pubmed
    The large multidomain Kalirin and Trio proteins containing dual Rho GTPase guanine nucleotide exchange factor (GEF) domains have been implicated in the regulation of neuronal fiber extension and pathfinding during development...
  27. Trembley J, Chen Z, Rodrigues C, Kren B, Steer C. Genomic organization and promoter characterization of the rat cyclin B1 gene. Gene. 2000;255:93-104 pubmed
    b>Cyclin B1 is a key regulatory protein involved in cellular mitosis. We have cloned 1...
  28. Colomer V, Engelender S, Sharp A, Duan K, Cooper J, Lanahan A, et al. Huntingtin-associated protein 1 (HAP1) binds to a Trio-like polypeptide, with a rac1 guanine nucleotide exchange factor domain. Hum Mol Genet. 1997;6:1519-25 pubmed
    ..We called the protein Duo because it is closely related to the human protein Trio but is shorter...
  29. Owczarek S, Bang M, Berezin V. Neurexin-Neuroligin Synaptic Complex Regulates Schizophrenia-Related DISC1/Kal-7/Rac1 "Signalosome". Neural Plast. 2015;2015:167308 pubmed publisher
    ..Our results indicate that the NX/NL synaptic complex is intrinsically involved in the regulation of DISC1 function, thus contributing to a better understanding of the pathology of schizophrenia. ..