Cloning and characterization of a human cDNA encoding a novel putative cytoplasmic protein-tyrosine-phosphatase

Takekawa, Mutsuhiro; Itoh, Fumio; Hinoda, Yuji; Arimura, Yoshiaki; Toyota, Minoru; Sekiya, Masuo; Adachi, Masaaki; Imai, Kohzoh; Yachi, Akira

doi:10.1016/0006-291x(92)92335-u

Cited by 35 publications

(18 citation statements)

References 22 publications

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“…They encode related receptor-linked PTPases with immunoglobulin and fibronectin domains in their extracellular regions and are involved in cell adhesion-dependent signaling pathways. The fourth most abundant clone, PTP-PEST, is a soluble cytoplasmic protein (16,20,21), the substrate of which was recently suggested to be p130 CAS (22,23), a Src and Crk-associated protein involved in Src-or Crk-mediated signaling. The third most abundant cDNA encoded a novel PTPase, designated PTP-TD14.…”

Section: Resultsmentioning

confidence: 99%

A Novel Putative Protein-tyrosine Phosphatase Contains a BRO1-like Domain and Suppresses Ha-ras-mediated Transformation

Cao¹,

Zhang²,

Ruiz‐Lozano³

et al. 1998

Journal of Biological Chemistry

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To investigate a potential role of protein-tyrosine phosphatases (PTPases) in myocardial growth and signaling, a degenerate primer-based reverse transcription-polymerase chain reaction approach was used to isolate cDNAs for proteins that contain a PTPase catalytic domain. Among the 16 cDNA clones isolated by reverse transcription-polymerase chain reaction from total neonatal rat cardiomyocyte RNA, one, designated PTP-TD14, was unique. Subsequent isolation and sequencing of a full-length PTP-TD14 cDNA confirmed that it encodes a novel 164-kDa protein, p164 PTP-TD14 . The C-terminal region contains the PTP-like domain, whereas the N-terminal region shows no homology to any known mammalian protein. However, this region is homologous to a yeast protein, BRO1, that is involved in the mitogen-activated protein kinase signaling pathway. Like BRO1, p164PTP-TD14 contains a proline-rich region with two putative SH3-domain binding sites. By Northern blot analysis, PTP-TD14 is expressed as a 5.3-kilobase pair transcript, not only in neonatal heart but also in many adult rat tissues. When expressed in either COS-7 or NIH-3T3 cells, p164 PTP-TD14 localizes to the cytoplasm in association with vesicle-like structures. Expression of p164 PTP-TD14 in NIH-3T3 cells inhibits Haras-mediated transformation more than 3-fold. This inhibitory activity is localized to the C-terminal PTPase homology domain, since no inhibition of Ha-ras-mediated focus formation was observed with a PTP-TD14 mutant, in which the putative catalytic activity was presumably inactivated by a point mutation. These findings indicate that PTP-TD14 encodes a novel protein that may be critically involved in regulating Ha-ras-dependent cell growth.

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Section: Resultsmentioning

confidence: 99%

A Novel Putative Protein-tyrosine Phosphatase Contains a BRO1-like Domain and Suppresses Ha-ras-mediated Transformation

Cao¹,

Zhang²,

Ruiz‐Lozano³

et al. 1998

Journal of Biological Chemistry

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“…Protein tyrosine phosphatase (PTP)-PEST is a ubiquitously expressed cytosolic PTP that is named for its proline-glutamine-serine-threonine-rich motifs (PEST sequences) (19,35,41,42). The tightly regulated activity of PTP-PEST plays instrumental roles in focal adhesion breakdown, cell spreading, and cell motility (1,14,19).…”

mentioning

confidence: 99%

Ras-Induced and Extracellular Signal-Regulated Kinase 1 and 2 Phosphorylation-Dependent Isomerization of Protein Tyrosine Phosphatase (PTP)-PEST by PIN1 Promotes FAK Dephosphorylation by PTP-PEST

Zheng

Yang

Xia

et al. 2011

Molecular and Cellular Biology

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Protein tyrosine phosphatase (PTP)-PEST is a critical regulator of cell adhesion and migration. However, the mechanism by which PTP-PEST is regulated in response to oncogenic signaling to dephosphorylate its substrates remains unclear. Here, we demonstrate that activated Ras induces extracellular signal-regulated kinase 1 and 2-dependent phosphorylation of PTP-PEST at S571, which recruits PIN1 to bind to PTP-PEST. Isomerization of the phosphorylated PTP-PEST by PIN1 increases the interaction between PTP-PEST and FAK, which leads to the dephosphorylation of FAK Y397 and the promotion of migration, invasion, and metastasis of v-H-Ras-transformed cells. These findings uncover an important mechanism for the regulation of PTP-PEST in activated Ras-induced tumor progression.Most cancer deaths are due to tumor invasion and metastasis rather than to primary tumors. Thus, understanding the fundamental mechanisms underlying tumor cell migration, invasion, and metastasis holds the promise of improving therapeutic approaches for cancer (7). Activating mutations of Ras, a small GTP-binding protein, occur in ϳ30% of human cancers and promote tumor progression (32). Accordingly, considerable effort has been expended in understanding the functions of Ras proteins in tumor cell migration, invasion, and metastasis (6).Cell migration is a highly coordinated and dynamic multistep process of leading-edge protrusion, focal adhesion turnover, tractional force generation, and tail retraction and detachment, all of which involve precise regulation of cell-cell adhesion and cell-to-extracellular matrix adhesion. Focal adhesions are specific regions of cells that make close contact with the extracellular matrix (30,44). Functional regulation of the molecules involved in focal adhesion signaling is a key component of tumor cell motility.Focal adhesion kinase (FAK) is a ubiquitously expressed nonreceptor protein tyrosine kinase that localizes at focal adhesions, mediates signaling induced by integrins, and plays an important role in many cellular functions (26, 27). Activated FAK, marked by autophosphorylation at Y397, recruits a number of SH2 and SH3 domain-containing proteins, including c-Src. The binding of c-Src to FAK is proposed to disrupt the intramolecular interaction between the c-Src SH2 domain and the negative regulatory carboxy-terminal Y529. Activated Src, in turn, phosphorylates FAK and further enhances FAK activity, thereby forming a positive feedback loop leading to the activation of downstream signaling molecules, such as extracellular signal-regulated kinase 1 and 2 (ERK1/2) and phosphatidylinositol 3-kinase (PI3-K)/AKT (17,29). FAK can exert control over the rate of focal adhesion turnover and, therefore, cell motility (29). FAK is a positive regulator of normal cell migration, and its overexpression or activation has been shown to promote cancer cell metastasis of some tumor types (17,29). However, accumulated evidence shows that in response to certain oncogenic signals, FAK negatively regulates cancer cell migration and...

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“…PTP-PEST is a ubiquitously expressed mammalian, cytosolic protein tyrosine phosphatase (PTP) 1 that was cloned in our laboratory (1) and by others (2)(3)(4). Several signaling proteins have been shown to be capable of binding to PTP-PEST, including Shc (5,6), paxillin (7), Grb2 (8), and Csk (9), but the physiological significance of these interactions and their relevance to the function of PTP-PEST is unclear.…”

mentioning

confidence: 99%

Regulation of Fibroblast Motility by the Protein Tyrosine Phosphatase PTP-PEST

Garton¹,

Tonks

1999

Journal of Biological Chemistry

126

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The protein tyrosine phosphatase PTP-PEST is a cytosolic enzyme that displays a remarkable degree of selectivity for tyrosine-phosphorylated p130Cas as a substrate, both in vitro and in intact cells. We have investigated the physiological role of PTP-PEST using Rat1 fibroblast-derived stable cell lines that we have engineered to overexpress PTP-PEST. These cell lines exhibit normal levels of tyrosine phosphorylation of the majority of proteins but have significantly lower levels of tyrosine phosphorylation of p130Cas than control cells. Initial cellular events occurring following integrin-mediated attachment to fibronectin (cell attachment and spreading) are essentially unchanged in cells overexpressing PTP-PEST; similarly, the extent and time course of mitogen-activated protein kinase activation in response to integrin engagement is unchanged. Cas and regulating cell migration.PTP-PEST is a ubiquitously expressed mammalian, cytosolic protein tyrosine phosphatase (PTP) 1 that was cloned in our laboratory (1) and by others (2-4). Several signaling proteins have been shown to be capable of binding to PTP-PEST, including Shc (5, 6), paxillin (7), Grb2 (8), and Csk (9), but the physiological significance of these interactions and their relevance to the function of PTP-PEST is unclear. In order to investigate the physiological substrate specificity of members of the PTP family, we developed a novel method involving expression of substrate-trapping mutant forms of PTPs (10, 11). These mutants retain a high affinity for substrates but are catalytically impaired. Therefore, they form complexes with appropriate target substrates that are amenable to isolation and characterization. We have used this method to identify substrates of PTP-PEST and thus gain insight into its physiological function. We have shown that the adaptor protein p130Cas is a specific substrate for PTP-PEST in vitro and in intact cells (11). Similar results have also been obtained in studies performed on fibroblasts derived from PTP-PESTϪ/Ϫ mice (12). This high degree of selectivity of PTP-PEST for p130Cas is derived from two distinct high affinity interactions. The catalytic domain of PTP-PEST itself displays intrinsic specificity for tyrosine-phosphorylated p130Cas (11), but this specificity is greatly enhanced by an interaction between the SH3 domain of p130Cas and a proline-rich sequence surrounding Pro-337 in the phosphatase (13). These data strongly suggest that a major role of PTP-PEST is to regulate the level of tyrosine phosphorylation of p130Cas within the cell. p130Cas was initially identified as a major tyrosine-phosphorylated protein in cells transformed by the oncogenes v-crk (14, 15) and v-src (16, 17). In addition, p130Cas is rapidly phosphorylated following mitogenic stimulation by a wide variety of agonists (18 -22), during B-cell activation via antigen receptor ligation (23,24), and following cell attachment to fibronectin (25)(26)(27)(28)(29). Although these observations implicate tyrosine phosphorylation of p130Cas in the contro...

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Cloning and characterization of a human cDNA encoding a novel putative cytoplasmic protein-tyrosine-phosphatase

Cited by 35 publications

References 22 publications

A Novel Putative Protein-tyrosine Phosphatase Contains a BRO1-like Domain and Suppresses Ha-ras-mediated Transformation

A Novel Putative Protein-tyrosine Phosphatase Contains a BRO1-like Domain and Suppresses Ha-ras-mediated Transformation

Ras-Induced and Extracellular Signal-Regulated Kinase 1 and 2 Phosphorylation-Dependent Isomerization of Protein Tyrosine Phosphatase (PTP)-PEST by PIN1 Promotes FAK Dephosphorylation by PTP-PEST

Regulation of Fibroblast Motility by the Protein Tyrosine Phosphatase PTP-PEST

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