Regulation of growth factor-induced signaling by protein-tyrosine-phosphatases.
The binding of a growth factor to its specific receptor catalyzes a complex cascade of intracellular signaling events, characterized by changes in the phosphorylation state of many key proteins. Among these phosphorylation events, tyrosine phosphorylation plays a prominent role in the transmission of postreceptor signals. The state of tyrosine phosphorylation is regulated by the actions of protein-tyrosine kinases (PTKs) and protein-tyrosine-phosphatases (PTPs). Dysregulation of either event can lead to abnormal cellular responses. PTPs generally act to regulate negatively-that is, to turn off-any signals generated by PTKs. However, this is not always the case, as seen by the phosphatase SHP-2, which can either be a positive or negative regulator of signal transduction depending on the particular cellular context. In addition, a novel family of dual specificity phosphatases has been recently discovered. These enzymes are capable of dephosphorylating phosphotyrosine and phosphothreonine/phosphoserine residues, and seem to play a significant role in attenuating the action of MAP kinases. Several themes appear throughout PTP regulation of growth factor signaling, including positive or negative regulation, importance of cell/ tissue type, identity of the receptor activated, and subcellular localization. Although only a handful of PTPs have been identified, the present work done in elucidating their function has revealed their significance in the maintenance of normal physiological responses to growth factors.
Byon
J C
JC
Department of Physiology, Tulane University Medical Center, New Orleans, Louisiana 70112-2699, USA.
Kenner
K A
KA
Kusari
A B
AB
Kusari
J
J
D000818:Animals; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins; D017493:Leukocyte Common Antigens / Q000502:physiology; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry / Q000502:physiology*; D015398:Signal Transduction
D006133:Growth Substances; D007328:Insulin; D047908:Intracellular Signaling Peptides and Proteins; D017493:Leukocyte Common Antigens; C516724:PTPN11 protein, human; C509249:PTPN6 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases