Receptor protein tyrosine kinases and phosphatases.
It is clear that the number of receptor PTKs and PTPs encoded by a typical vertebrate genome is rather large. Although the signal pathways activated by the receptor PTKs may in many cases be common, specificity is provided by the ligand-binding domain and the availability of ligand. In addition, the precise spectrum of substrates that bind to and are phosphorylated by each receptor PTK can differ based on the number and nature of the autophosphorylation sites and on the repertoire of SH2-containing proteins and other substrates expressed in each cell type. It is also clear that receptor PTKs can activate multiple independent signaling pathways and that the output of these pathways can be integrated to provide a specific cellular response. The role of receptor PTPs in such integrated signaling networks is not yet obvious. In some cases, they may activate nonreceptor PTKs, whereas in other cases, they may counteract the effects of activated receptor and nonreceptor PTKs by dephosphorylating the PTKs themselves or their substrates. We know very little about the substrate specificity of PTPs, but in part this must be dictated by their subcellular location. It is possible that there are specific pairs of receptor PTKs and PTPs, which act in concert at the cell surface to activate and down-regulate specific signal pathways. Progress in understanding the function of receptor PTPs will depend on identifying ligands for receptor PTPs and then determining how ligand binding influences their activity.
Hunter
T
T
Molecular Biology and Virology Laboratory, Salk Institute, San Diego, California 92186.
Lindberg
R A
RA
Middlemas
D S
DS
Tracy
S
S
van der Geer
P
P
D000818:Animals; D006801:Humans; D008565:Membrane Proteins / Q000502:physiology; D010802:Phylogeny; D017027:Protein Tyrosine Phosphatases / Q000502:physiology*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000502:physiology*; D020801:Receptor, Ciliary Neurotrophic Factor; D036104:Receptor, EphA2; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000502:physiology; D011956:Receptors, Cell Surface / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology
D008565:Membrane Proteins; D020801:Receptor, Ciliary Neurotrophic Factor; D011956:Receptors, Cell Surface; D020794:Receptor Protein-Tyrosine Kinases; D036104:Receptor, EphA2; D016186:Receptor, Macrophage Colony-Stimulating Factor; D017027:Protein Tyrosine Phosphatases