PTP1B regulates neurite extension mediated by cell-cell and cell-matrix adhesion molecules.
N-cadherin and beta1-integrin adhesion and signaling play important roles in growth cone adhesion and guidance. Each of these adhesion receptor systems is composed of multiprotein complexes, and both adhesion and downstream signaling events are regulated through the interaction of protein tyrosine kinases and phosphatases with many of the proteins that make up these complex systems. Work from our laboratory reported that the nonreceptor protein tyrosine phosphatase PTP1B is localized to adherens junctions and focal adhesion complexes and regulates both N-cadherin- and beta1-integrin-mediated adhesion. PTP1B appears to modulate integrin-mediated adhesion through regulation of src activation and cadherin-mediated adhesion through dephosphorylation of beta-catenin. We have continued these studies and report that PTP1B is localized to the tips of growing neurites and that introduction of a noncatalytic mutant of PTP1B into PC12 cells results in inhibition of N-cadherin- and beta1-integrin-mediated neurite outgrowth but is without effect on neurite outgrowth on poly-L-lysine. Moreover, suppressing the level of PTP1B in primary embryonic chick neural retina cells using antisense oligonucleotides also inhibits N-cadherin- and beta1-integrin-mediated neurite outgrowth. Neither of these techniques reduces the levels of expression of either adhesion receptor. We conclude that PTP1B is a regulatory component of the molecular complex required for both N-cadherin and beta1-integrin-mediated axon growth.
Pathre
P
P
Department of Biological Sciences, Wayne State University, Detroit, Michigan, USA.
Arregui
C
C
Wampler
T
T
Kue
I
I
Leung
T C
TC
Lilien
J
J
Balsamo
J
J
D000818:Animals; D015820:Cadherins / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology*; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology*; D002490:Central Nervous System / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D002642:Chick Embryo; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D005109:Extracellular Matrix / Q000378:metabolism*; D049452:Green Fluorescent Proteins; D007202:Indicators and Reagents / Q000378:metabolism; D019012:Integrin beta1 / Q000378:metabolism; D008164:Luminescent Proteins / Q000235:genetics; D009154:Mutation / Q000502:physiology; D016501:Neurites / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D016716:PC12 Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D012160:Retina / Q000187:drug effects / Q000196:embryology / Q000378:metabolism
D015820:Cadherins; D007202:Indicators and Reagents; D019012:Integrin beta1; D008164:Luminescent Proteins; D016376:Oligonucleotides, Antisense; D049452:Green Fluorescent Proteins; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases; C516610:Ptpn1 protein, rat