Computational analysis of isoform-specific signal regulation by CEACAM1-A cell adhesion molecule expressed in PC12 cells.
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.
Obrink
Björn
B
Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden. bjorn.obrink@cmb.ki.se
Sawa
Hiroki
H
Scheffrahn
Inka
I
Singer
Bernhard B
BB
Sigmundsson
Kristmundur
K
Sundberg
Ulla
U
Heymann
Robert
R
Beauchemin
Nicole
N
Weng
Gehzi
G
Ram
Prahlad
P
Iyengar
Ravi
R
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
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