Cell-cell adhesion mediated by binding of membrane-anchored ligand LERK-2 to the EPH-related receptor human embryonal kinase 2 promotes tyrosine kinase activity.
Human embryonal kinase 2 (HEK2) is a protein-tyrosine kinase that is a member of the EPH family of receptors. Transcripts for HEK2 have a wide tissue distribution. Recently, a still growing family of ligands, which we have named LERKs, for ligands of the eph-related kinases, has been isolated. In order to analyze functional effects between the LERKs and the HEK2 receptor, we expressed HEK2 cDNA in an interleukin-3-dependent progenitor cell line 32D that grows as single cells in culture. Within the group of LERKs, LERK-2 and -5 were shown to bind to HEK2. Membrane-bound and soluble forms of LERK-2 were demonstrated to signal through HEK2 as judged by receptor phosphorylation. Coincubation of HEK2 and LERK-2 expressing cells induced cell-cell adhesion and formation of cell aggregates. This interaction could be inhibited by preincubation of HEK2 expressing cells with soluble LERK-2. Coexpression of HEK2 and LERK-2 in 32D cells showed reduced kinase activity and autophosphorylation of HEK2 compared with the juxtacrine stimulation, which seems to be due to a reduced sensitivity of the receptor.
Böhme
B
B
Chemotherapeutisches Forschungsinstitut, Georg-Speyer-Haus, 60596 Frankfurt, Federal Republic of Germany.
VandenBos
T
T
Cerretti
D P
DP
Park
L S
LS
Holtrich
U
U
Rübsamen-Waigmann
H
H
Strebhardt
K
K
D000818:Animals; D001483:Base Sequence; D002448:Cell Adhesion; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D003470:Culture Media; D004789:Enzyme Activation; D036387:Ephrin-B1; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D010766:Phosphorylation; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D036223:Receptor, EphB3
D003470:Culture Media; D036387:Ephrin-B1; D009838:Oligodeoxyribonucleotides; D011506:Proteins; D020794:Receptor Protein-Tyrosine Kinases; D036223:Receptor, EphB3