ErbB-2 and met reciprocally regulate cellular signaling via plexin-B1.
Sema4D-induced activation of plexin-B1 has been reported to evoke different and sometimes opposing cellular responses. The mechanisms underlying the versatility of plexin-B1-mediated effects are not clear. Plexin-B1 can associate with the receptor tyrosine kinases ErbB-2 and Met. Here we show that Sema4D-induced activation and inactivation of RhoA require ErbB-2 and Met, respectively. In breast carcinoma cells, Sema4D can have pro- and anti-migratory effects depending on the presence of ErbB-2 and Met, and the exchange of the two receptor tyrosine kinases is sufficient to convert the cellular response to Sema4D from pro- to anti-migratory and vice versa. This work identifies a novel mechanism by which plexin-mediated signaling can be regulated and explains how Sema4D can exert different biological activities through the differential association of its receptor with ErbB-2 and Met.
Swiercz
Jakub M
JM
Institute of Pharmacology, University of Heidelberg, Im Neuenheimer Feld 366, 69120 Heidelberg, Germany.
Worzfeld
Thomas
T
Offermanns
Stefan
S
D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D006801:Humans; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D019859:Proto-Oncogene Proteins c-met; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D017978:Receptors, Growth Factor / Q000235:genetics / Q000378:metabolism; D039961:Semaphorins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D020742:rhoA GTP-Binding Protein / Q000235:genetics / Q000378:metabolism
D015703:Antigens, CD; D009419:Nerve Tissue Proteins; D011518:Proto-Oncogene Proteins; D019859:Proto-Oncogene Proteins c-met; D018719:Erb-b2 Receptor Tyrosine Kinases; D011956:Receptors, Cell Surface; D017978:Receptors, Growth Factor; D039961:Semaphorins; D020742:rhoA GTP-Binding Protein; C093224:CD100 antigen; C492119:PLXNB1 protein, human; C066737:RHOA protein, human; C491743:MET protein, human