ROLE OF JAM-1 IN CELL ADHESION AND MIGRATION

Summary

Principal Investigator: Ulhas P Naik
Affiliation: University of Delaware
Country: USA
Abstract: DESCRIPTION (Adapted from the Applicant's Abstract): Dr. Naik and his colleagues previously characterized a platelet membrane glycoprotein which was specifically recognized by a stimulatory monoclonal antibody. Crosslinking of this receptor lead to the activation of platelets resulting in platelet aggregation and secretion. They have now cloned the complete cDNA of this receptor. The deduced amino acid sequence shows significant homology to a mouse junctional adhesion molecule and to other cell adhesion molecules belonging to the Ig superfamily. This protein, which is named Junctional Adhesion Molecule 1 (JAM-1), has two Ig-like domains, a transmembrane domain, and a short cytoplasmic domain. Interestingly, JAM-1 is expressed on various cells of the cardiovascular system including platelets, endothelial cells and leukocytes. They found that overexpression of JAM-1 induces endothelial cell proliferation and migration. This JAM-1 induced endothelial cell migration is specific to integrin alphaVbeta3, the vitronectin receptor. Northern and Western blot analysis show the predominant expression of a higher form of JAM-1 on these cells. The specific aims of this project are: 1) To determine the role of JAM-1 in cell adhesion and migration. 2) cDNA cloning and characterization of the higher molecular form of JAM-1. 3) Identification of the physiological ligand/receptor that binds JAM-1 or its higher form. 4) To determine the signaling pathway induced through JAM-1. Dr. Naik will express recombinant JAM-1 in CHO cells to determine the role of JAM-1 in cell adhesion. Understanding the role of JAM-1 in cell adhesion and migration is the focus of this proposal. Priorities will be given to the studies that involve cloning of cDNA of the higher form of JAM-1, and identification of the physiological ligand to this novel cell adhesion molecule. They will use platelet functional studies as tools to elucidate the various steps of the signal transduction pathway induced through JAM-1. These steps include intracellular Ca2+ increase, protein kinase activation, protein phosphorylation, granular secretion, and activation of integrin alpha IIb beta3. Various specific inhibitors of each of these steps will be used. These signaling events will be then confirmed in other cell types. The results obtained will help to determine the signaling pathway induced through JAM-1 and the role of JAM-1 or its homologue in the process of cell adhesion, migration, angiogenesis, and tissue architecture. Characterizing the cell adhesion function of this novel protein will open up a new line of investigation that is important in inflammatory diseases and vascular biology.
Funding Period: 2000-08-15 - 2005-07-31
more information: NIH RePORT

Top Publications

  1. pmc Junctional adhesion molecule-A suppresses platelet integrin αIIbβ3 signaling by recruiting Csk to the integrin-c-Src complex
    Meghna U Naik
    Delaware Cardiovascular Research Center, and
    Blood 123:1393-402. 2014
  2. pmc Junctional adhesion molecule-A regulates vascular endothelial growth factor receptor-2 signaling-dependent mouse corneal wound healing
    Sharmila Chatterjee
    Department of Biological Sciences, University of Delaware, Newark, Delaware, United States of America
    PLoS ONE 8:e63674. 2013
  3. pmc A spatial model for integrin clustering as a result of feedback between integrin activation and integrin binding
    Erik S Welf
    Department of Chemical Engineering, University of Delaware, Newark, Delaware, USA
    Biophys J 103:1379-89. 2012
  4. pmc JAM-A protects from thrombosis by suppressing integrin αIIbβ3-dependent outside-in signaling in platelets
    Meghna U Naik
    Department of Biological Sciences, University of Delaware, Newark, DE 19716, USA
    Blood 119:3352-60. 2012
  5. pmc Putting the brakes on cancer cell migration: JAM-A restrains integrin activation
    Ulhas P Naik
    Department of Biological Sciences, Delaware Biotechnology Institute, University of Delaware, Newark, Delaware 19716, USA
    Cell Adh Migr 2:249-51. 2008
  6. doi Attenuation of junctional adhesion molecule-A is a contributing factor for breast cancer cell invasion
    Meghna U Naik
    Deparment of Biological Sciences, University of Delaware, Newark, DE 19716, USA
    Cancer Res 68:2194-203. 2008
  7. ncbi Junctional adhesion molecules in angiogenesis
    Tejal U Naik
    Charter School of Wilmington, Delaware, USA
    Front Biosci 13:258-62. 2008
  8. ncbi Deletion of JAM-A causes morphological defects in the corneal epithelium
    Liang I Kang
    Department of Biological Sciences, University of Delaware, Newark, DE 19716, USA
    Int J Biochem Cell Biol 39:576-85. 2007
  9. ncbi Fibroblast growth factor-2 failed to induce angiogenesis in junctional adhesion molecule-A-deficient mice
    Vesselina G Cooke
    Department of Biological Sciences, University of Delaware, Newark, DE 19716, USA
    Arterioscler Thromb Vasc Biol 26:2005-11. 2006
  10. ncbi Junctional adhesion molecule-A-induced endothelial cell migration on vitronectin is integrin alpha v beta 3 specific
    Meghna U Naik
    Department of Biological Sciences, University of Delaware, Newark, DE 19716, USA
    J Cell Sci 119:490-9. 2006

Scientific Experts

  • Ulhas P Naik
  • Meghna U Naik
  • Melinda K Duncan
  • Vesselina G Cooke
  • Tejal U Naik
  • Sharmila Chatterjee
  • Erik S Welf
  • Yan Wang
  • Arthur T Suckow
  • Liang I Kang
  • James J Parris
  • Jeffrey L Caplan
  • Timothy J Stalker
  • Babatunde A Ogunnaike
  • Lawrence F Brass
  • Kirk J Czymmek
  • William C Skarnes

Detail Information

Publications11

  1. pmc Junctional adhesion molecule-A suppresses platelet integrin αIIbβ3 signaling by recruiting Csk to the integrin-c-Src complex
    Meghna U Naik
    Delaware Cardiovascular Research Center, and
    Blood 123:1393-402. 2014
    ..Upon agonist stimulation, JAM-A is dephosphorylated on the tyrosine, allowing the dissociation of Csk from the integrin complex, and thus facilitating outside-in signaling. ..
  2. pmc Junctional adhesion molecule-A regulates vascular endothelial growth factor receptor-2 signaling-dependent mouse corneal wound healing
    Sharmila Chatterjee
    Department of Biological Sciences, University of Delaware, Newark, Delaware, United States of America
    PLoS ONE 8:e63674. 2013
    ..Our results suggest that in the absence of Jam-A, the VEGF-A/VEGFR-2 pathway is upregulated, thereby augmenting wound induced corneal inflammation, angiogenesis, and myofibroblast accumulation leading to scarring...
  3. pmc A spatial model for integrin clustering as a result of feedback between integrin activation and integrin binding
    Erik S Welf
    Department of Chemical Engineering, University of Delaware, Newark, Delaware, USA
    Biophys J 103:1379-89. 2012
    ....
  4. pmc JAM-A protects from thrombosis by suppressing integrin αIIbβ3-dependent outside-in signaling in platelets
    Meghna U Naik
    Department of Biological Sciences, University of Delaware, Newark, DE 19716, USA
    Blood 119:3352-60. 2012
    ..We conclude that JAM-A normally limits platelet accumulation by inhibiting integrin outside-in signaling thus preventing premature platelet activation...
  5. pmc Putting the brakes on cancer cell migration: JAM-A restrains integrin activation
    Ulhas P Naik
    Department of Biological Sciences, Delaware Biotechnology Institute, University of Delaware, Newark, Delaware 19716, USA
    Cell Adh Migr 2:249-51. 2008
    ..The molecular mechanism of this function of JAM-A is beyond its well-characterized barrier function at the tight junction. Our results point out that JAM-A differentially regulates migration of endothelial and cancer cells...
  6. doi Attenuation of junctional adhesion molecule-A is a contributing factor for breast cancer cell invasion
    Meghna U Naik
    Deparment of Biological Sciences, University of Delaware, Newark, DE 19716, USA
    Cancer Res 68:2194-203. 2008
    ..Furthermore, loss of JAM-A could be used as a biomarker for aggressive breast cancer...
  7. ncbi Junctional adhesion molecules in angiogenesis
    Tejal U Naik
    Charter School of Wilmington, Delaware, USA
    Front Biosci 13:258-62. 2008
    ..This review focuses on a recently identified novel cell adhesion molecule, Junctional Adhesion Molecule A, and its role in the process of regulating angiogenesis...
  8. ncbi Deletion of JAM-A causes morphological defects in the corneal epithelium
    Liang I Kang
    Department of Biological Sciences, University of Delaware, Newark, DE 19716, USA
    Int J Biochem Cell Biol 39:576-85. 2007
    ..In summary, JAM-A is expressed in the corneal epithelium where it appears to regulate cell shape...
  9. ncbi Fibroblast growth factor-2 failed to induce angiogenesis in junctional adhesion molecule-A-deficient mice
    Vesselina G Cooke
    Department of Biological Sciences, University of Delaware, Newark, DE 19716, USA
    Arterioscler Thromb Vasc Biol 26:2005-11. 2006
    ..Whether JAM-A is involved in FGF-2-induced angiogenesis in vivo is not known. We used JAM-A null mice to conclusively determine the role of JAM-A in FGF-2-induced neovascularization...
  10. ncbi Junctional adhesion molecule-A-induced endothelial cell migration on vitronectin is integrin alpha v beta 3 specific
    Meghna U Naik
    Department of Biological Sciences, University of Delaware, Newark, DE 19716, USA
    J Cell Sci 119:490-9. 2006
    ..Taken together, these results suggest that signaling through JAM-A is necessary for alpha(v)beta(3)-dependent HUVEC migration and implicate JAM-A in the regulation of vascular function...
  11. ncbi JAM-A expression during embryonic development
    James J Parris
    Department of Biological Sciences, University of Delaware, Newark, Delaware 19716, USA
    Dev Dyn 233:1517-24. 2005
    ..Thus, JAM-A is prominently expressed in embryonic vasculature and the epithelial components of several organ systems and may have an important role in their development...