Microtubule and Cell Contact Dependency of ER-bound PTP1B Localization in Growth Cones

PTP1B is an ER-bound protein tyrosine phosphatase implied in the regulation of cell adhesion. Here we investigated mechanisms involved in the positioning and dynamics of PTP1B in axonal growth cones and evaluated the role of this enzyme in axons. In growth cones, PTP1B consistently localizes in the central domain, and occasionally at the peripheral region and filopodia. Live imaging of GFP-PTP1B reveals dynamic excursions of fingerlike processes within the peripheral region and filopodia. PTP1B and GFP-PTP1B colocalize with ER markers and coalign with microtubules at the peripheral region and redistribute to the base of the growth cone after treatment with nocodazole, a condition that is reversible. Growth cone contact with cellular targets is accompanied by invasion of PTP1B and stable microtubules in the peripheral region aligned with the contact axis. Functional impairment of PTP1B causes retardation of axon elongation, as well as reduction of growth cone filopodia lifetime and Src activity. Our results highlight the role of microtubules and cell contacts in the positioning of ER-bound PTP1B to the peripheral region of growth cones, which may be required for the positive role of PTP1B in axon elongation, filopodia stabilization, and Src activity.

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SRC binding to the cytoskeleton, triggered by growth cone attachment to laminin, is protein tyrosine phosphatase-dependent

Journal of Cell Science ◽

10.1242/jcs.111.16.2465 ◽

1998 ◽

Vol 111 (16) ◽

pp. 2465-2475 ◽

Cited By ~ 3

Author(s):

S. Helmke ◽

K. Lohse ◽

K. Mikule ◽

M.R. Wood ◽

K.H. Pfenninger

Keyword(s):

Phosphatase Activity ◽

Growth Cone ◽

Protein Tyrosine Phosphatase ◽

Tyrosine Phosphatase ◽

Protein Tyrosine Phosphatases ◽

Growth Cones ◽

Tyrosine Phosphatases ◽

Protein Tyrosine ◽

Adhesion Sites ◽

Adhesion Site

The interaction of the non-receptor tyrosine kinase, Src, with the cytoskeleton of adhesion sites was studied in nerve growth cones isolated from fetal rat brain. Of particular interest was the role of protein tyrosine phosphatases in the regulation of Src-cytoskeleton binding. Growth cones were found to contain a high level of protein tryrosine phosphatase activity, most of it membrane-associated and forming large, multimeric and wheat germ agglutinin-binding complexes. The receptor tyrosine phosphatase PTPalpha seems to be the most prevalent species among the membrane-associated enzymes. As seen by immunofluorescence, PTPalpha is present throughout the plasmalemma of the growth cone including filopodia, and it forms a punctate pattern consistent with that of integrin beta1. For adhesion site analysis, isolated growth cones were either plated onto the neurite growth substratum, laminin, or kept in suspension. Plating growth cones on laminin triggered an 8-fold increase in Src binding to the adherent cytoskeleton. This effect was blocked completely with the protein tyrosine phosphatase inhibitor, vanadate. Growth cone plating also increased the association with adhesion sites of tyrosine phosphatase activity (14-fold) and of PTPalpha immunoreactivity (6-fold). Vanadate blocked the enzyme activity but not the recruitment of PTPalpha to the adhesion sites. In conjunction with our previous results on growth cones, these data suggest that integrin binding to laminin triggers the recruitment of PTPalpha (and perhaps other protein tyrosine phosphatases) to adhesion sites, resulting in de-phosphorylation of Src's tyr 527. As a result Src unfolds, becomes kinase-active, and its SH2 domain can bind to an adhesion site protein. This implies a critical role for protein tyrosine phosphatase activity in the earliest phases of adhesion site assembly.

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Characterization of protein tyrosine phosphatase SH-PTP2. Study of phosphopeptide substrates and possible regulatory role of SH2 domains.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(17)37504-x ◽

1994 ◽

Vol 269 (8) ◽

pp. 5602-5611 ◽

Cited By ~ 2

Author(s):

U. Dechert ◽

M. Adam ◽

K.W. Harder ◽

I. Clark-Lewis ◽

F. Jirik

Keyword(s):

Protein Tyrosine Phosphatase ◽

Tyrosine Phosphatase ◽

Regulatory Role ◽

Protein Tyrosine ◽

Sh2 Domains

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The role of vascular endothelial protein tyrosine phosphatase on nitric oxide synthase function in diabetes: from molecular biology to the clinic

Journal of Cell Communication and Signaling ◽

10.1007/s12079-021-00611-9 ◽

2021 ◽

Author(s):

Alberto Fernando Oliveira Justo ◽

Pedro Paulo Luciano Afonso

Keyword(s):

Nitric Oxide ◽

Nitric Oxide Synthase ◽

Molecular Biology ◽

Protein Tyrosine Phosphatase ◽

Tyrosine Phosphatase ◽

Vascular Endothelial ◽

Protein Tyrosine ◽

Oxide Synthase

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Formation of smooth muscle α actin filaments in CD34+ bone marrow cells on arterial elastic laminae: Potential role of SH2 domain-containing protein tyrosine phosphatase-1

Matrix Biology ◽

10.1016/j.matbio.2008.01.001 ◽

2008 ◽

Vol 27 (4) ◽

pp. 282-294 ◽

Cited By ~ 4

Author(s):

S LIU ◽

B TEFFT ◽

A ZHANG ◽

L ZHANG ◽

Y WU

Keyword(s):

Bone Marrow ◽

Smooth Muscle ◽

Protein Tyrosine Phosphatase ◽

Actin Filaments ◽

Potential Role ◽

Bone Marrow Cells ◽

Tyrosine Phosphatase ◽

Sh2 Domain ◽

Elastic Laminae

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Role of Chondroitin Sulfate (CS) Modification in the Regulation of Protein-tyrosine Phosphatase Receptor Type Z (PTPRZ) Activity

Journal of Biological Chemistry ◽

10.1074/jbc.m116.742536 ◽

2016 ◽

Vol 291 (35) ◽

pp. 18117-18128 ◽

Cited By ~ 22

Author(s):

Kazuya Kuboyama ◽

Akihiro Fujikawa ◽

Ryoko Suzuki ◽

Naomi Tanga ◽

Masaharu Noda

Keyword(s):

Chondroitin Sulfate ◽

Protein Tyrosine Phosphatase ◽

Tyrosine Phosphatase ◽

Receptor Type ◽

Protein Tyrosine

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AP-1 elements and TCL1 protein regulate expression of the gene encoding protein tyrosine phosphatase PTPROt in leukemia

Blood ◽

10.1182/blood-2011-01-323147 ◽

2011 ◽

Vol 118 (23) ◽

pp. 6132-6140 ◽

Cited By ~ 13

Author(s):

Tasneem Motiwala ◽

Nicola Zanesi ◽

Jharna Datta ◽

Satavisha Roy ◽

Huban Kutay ◽

...

Keyword(s):

Protein Tyrosine Phosphatase ◽

Tyrosine Phosphatase ◽

Lymphocytic Leukemia ◽

Potential Mechanism ◽

Wild Type ◽

Truncated Form ◽

Gene Encoding ◽

Protein Tyrosine ◽

Encoding Protein

Abstract We previously demonstrated that the gene encoding PTPROt, the truncated form of protein tyrosine phosphatase receptor type O expressed predominantly in hematopoietic cells, is a candidate tumor suppressor and is down-regulated in chronic lymphocytic leukemia (CLL). Here, we show that PTPROt expression is significantly reduced in CD19+ spleen B cells from Eμ-T cell leukemia 1 (TCL1) transgenic mice relative to the wild-type mice. Strikingly, as much as a 60% decrease in PTPROt expression occurs at 7 weeks independently of promoter methylation. To elucidate the potential mechanism for this early suppression of PTPROt in these mice, we explored the role of activating protein-1 (AP-1) in its expression. We first demonstrate that AP-1 activation by 12-O-tetradecanoylphorbol-13-acetate induces PTPROt expression with concurrent recruitment of c-fos and c-jun to its promoter. The PTPROt promoter is also responsive to over- and underexpression of AP-1, confirming the role of AP-1 in PTPROt expression. Next, we demonstrate that TCL1 can repress the PTPROt promoter by altering c-fos expression and c-jun activation state. Finally, using primary CLL cells we have shown an inverse relationship between TCL1 and PTPROt expression. These findings further substantiate the role of TCL1 in PTPROt suppression and its importance in the pathogenesis of CLL.

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