Dynamic modules and heterogeneity of function: a lesson from tyrosine kinase receptors in endothelial cells.
An important unresolved issue related to tyrosine kinase receptor signaling pathways is the lack of specificity of the molecular effectors involved. The specificity of the biological responses that are nevertheless elicited may be explained by differences in activation thresholds, as well as by temporal (transient versus sustained) and topographical aspects of receptor activation. On the basis of recent lessons from endothelial cells, we argue that an additional strategy can be adopted to generate specificity, i.e. tyrosine kinase receptors may form distinct signaling modules with other transmembrane proteins, such as adhesive receptors, to elicit different biological programs in stimulated cells.
Bussolino
F
F
Institute for Cancer Research and Treatment, University of Torino School of Medicine, 10060 Candiolo, Italy. fbussolino@ircc.unito.it
Serini
G
G
Mitola
S
S
Bazzoni
G
G
Dejana
E
E
D000818:Animals; D002448:Cell Adhesion; D002462:Cell Membrane / Q000378:metabolism; D004727:Endothelium / Q000166:cytology*; D006801:Humans; D008954:Models, Biological; D020794:Receptor Protein-Tyrosine Kinases / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology*; D017978:Receptors, Growth Factor / Q000378:metabolism; D040262:Receptors, Vascular Endothelial Growth Factor; D015398:Signal Transduction
D017978:Receptors, Growth Factor; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor