title: Computational analysis of isoform-specific signal regulation by CEACAM1-A cell adhesion molecule expressed in PC12 cells.
abstract: CEACAM1 is a signal-regulating, homophilic cell adhesion receptor system expressed in epithelia, vessel endothelia, and leukocytes. Here, we demonstrate that CEACAM1 is expressed also in PC12 cells, both as the common transmembrane isoforms, CEACAM1-L and CEACAM1-S, and as a novel, secreted, differentially spliced isoform. CEACAM1 can have both positive and negative effects on cell signaling. In an attempt to explain this dual behavior, we have initiated computational analysis of the signal-regulating effects of CEACAM1. This suggests that CEACAM1 can exert its signal-regulating activities by discriminating between binding of Src kinases and SHP phosphatases, respectively. Major factors that regulate this discrimination are the expression levels and expression ratios of transmembrane CEACAM1-L and CEACAM1-S, the concentration of secreted CEACAM1, and homophilic binding of CEACAM1 presented by neighboring cells.
authors.affiliation: Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden. bjorn.obrink@cmb.ki.se
authors.forename: Björn
authors.initials: B
authors.lastname: Obrink
authors.forename: Hiroki
authors.initials: H
authors.lastname: Sawa
authors.forename: Inka
authors.initials: I
authors.lastname: Scheffrahn
authors.forename: Bernhard B
authors.initials: BB
authors.lastname: Singer
authors.forename: Kristmundur
authors.initials: K
authors.lastname: Sigmundsson
authors.forename: Ulla
authors.initials: U
authors.lastname: Sundberg
authors.forename: Robert
authors.initials: R
authors.lastname: Heymann
authors.forename: Nicole
authors.initials: N
authors.lastname: Beauchemin
authors.forename: Gehzi
authors.initials: G
authors.lastname: Weng
authors.forename: Prahlad
authors.initials: P
authors.lastname: Ram
authors.forename: Ravi
authors.initials: R
authors.lastname: Iyengar
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D015703:Antigens, CD / Q000502:physiology*; D000943:Antigens, Differentiation / Q000502:physiology*; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules; D019295:Computational Biology / Q000379:methods*; D004305:Dose-Response Relationship, Drug; D047908:Intracellular Signaling Peptides and Proteins; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008956:Models, Chemical; D016716:PC12 Cells; D010766:Phosphorylation; D011485:Protein Binding; D020033:Protein Isoforms; D017434:Protein Structure, Tertiary; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; C069847:CD66 antigens; D015815:Cell Adhesion Molecules; D047908:Intracellular Signaling Peptides and Proteins; D020033:Protein Isoforms; D016392:Proto-Oncogene Proteins pp60(c-src); D020928:Mitogen-Activated Protein Kinases; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; C509250:Ptpn6 protein, rat