Protein tyrosine phosphatase PTP1B suppresses p210 bcr-abl-induced transformation of Rat-1 fibroblasts and promotes differentiation of K562 cells

The bcr-abl chimeric oncoprotein exhibits deregulated protein tyrosine kinase activity and is implicated in the pathogenesis of Philadelphia chromosome (Ph)-positive human leukemias, such as chronic myelogenous leukemia (CML). Recently we have shown that the levels of the protein tyrosine phosphatase PTP1B are enhanced in p210 bcr-abl-expressing cell lines. Furthermore, PTP1B recognizes p210 bcr-abl as a substrate, disrupts the formation of a p210 bcr-abl/Grb2 complex, and inhibits signaling events initiated by this oncoprotein PTK. In this report, we have examined whether PTP1B effects transformation induced by p210 bcr-abl. We demonstrate that expression of either wild-type PTP1B or the substrate-trapping mutant form of the enzyme (PTP1B-D181A) in p210 bcr-abl-transformed Rat-1 fibroblasts diminished the ability of these cells to form colonies in soft agar, to grow in reduced serum, and to form tumors in nude mice. In contrast, TCPTP, the closest relative of PTP1B, did not effect p210 bcr-abl-induced transformation. Furthermore, neither PTP1B nor TCPTP inhibited transformation induced by v-Abl. In addition, overexpression of PTP1B or treatment with CGP57148, a small molecule inhibitor of p210 bcr-abl, induced erythroid differentiation of K562 cells, a CML cell line derived from a patient in blast crisis. These data suggest that PTP1B is a selective, endogenous inhibitor of p210 bcr-abl and is likely to be important in the pathogenesis of CML.

Mutant forms of growth factor-binding protein-2 reverse BCR-ABL-induced transformation.

Growth factor-binding protein 2 (Grb2) is an adaptor protein that links tyrosine kinases to Ras. BCR-ABL is a tyrosine kinase oncoprotein that is implicated in the pathogenesis of Philadelphia chromosome (Ph1)-positive leukemias. Grb2 forms a complex with BCR-ABL and the nucleotide exchange factor Sos that leads to the activation of the Ras protooncogene. In this report we demonstrate that Grb2 mutant proteins lacking amino- or carboxyl-terminal src homology SH3 domains suppress BCR-ABL-induced Ras activation and reverse the oncogenic phenotype. The Grb2 SH3-deletion mutant proteins bind to BCR-ABL and do not impair tyrosine kinase activity. Expression of the Grb2 SH3-deletion mutant proteins in BCR-ABL-transformed Rat-1 fibroblasts and in the human Ph1-positive leukemic cell line K562 inhibits their ability to grow as foci in soft agar and form tumors in nude mice. Furthermore, expression of the Grb2 SH3-deletion mutants in K562 cells induced their differentiation. Because Ras plays an important role in signaling by receptor and nonreceptor tyrosine kinases, the use of interfering mutant Grb2 proteins may be applied to block the proliferation of other cancers that depend in part on activated tyrosine kinases for growth.

Engravings of a plan and an exterior view of Harvard Hall drawn by Pierre Eugène du Simitière, (photographic prints, photostats, and negative photostats), [ca. 1764]

The floor plan details all three floors of Harvard Hall, including its cellars, kitchen, chapel, and library. The items in this folder were reproduced from "The Burning of Harvard Hall, 1764, and its consequences," presented by F. Apthorp Foster at the April 1911 meeting of the Colonial Society of Massachusetts, and published in the Publications of the Colonial Society of Massachusetts, Volume XIV. The floor plan and exterior views were created by Pierre Eugène du Simitière in circa 1764. The original drawings are held in the Pierre Eugène du Simitière collection in the Ridgeway Branch of the Library Company of Philadelphia.

American spiders and their spinningwork. A natural history of the orbweaving spiders of the United States, with special regard to their industry and habits. By Henry C. McCook.

v.2 1890

American spiders and their spinningwork. A natural history of the orbweaving spiders of the United States, with special regard to their industry and habits. By Henry C. McCook.

v.3 1893

Miscellaneous legal documents, 1751-1840

Subpoenas for the sheriff of Philadelphia County to individuals to serve for actions relating to trespass on a case, ejectment, and replevin of three negro slaves.

American spiders and their spinningwork. A natural history of the orbweaving spiders of the United States, with special regard to their industry and habits. By Henry C. McCook.

v.3

American spiders and their spinningwork. A natural history of the orbweaving spiders of the United States, with special regard to their industry and habits. By Henry C. McCook.

v.2

Philadelphia, Pennsylvania, 1797 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: This plan of the city of Philadelphia and it's environs (shewing the improved parts) is dedicated to the mayor, aldermen and citizens thereof, by their most obedient servant John Hills surveyor and draughtsman ; May 30th 1796 ; engraved by John Cooke of Hendon Middlesex near London. It was Published and Sold by John Hills Surveyor and Draughsman in 1797. Scale [1:7,200]. The image inside the map neatline is georeferenced to the surface of the earth and fit to Pennsylvania South State Plane Coordinate System NAD83 (in Feet) (Fipszone 3702). All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map. This map shows features such as roads, drainage, built-up areas, selected public and private buildings, schools, churches, industry locations (e.g. mills, factories, mines, etc.), docks, fortification, ground cover, and more. Relief shown by hachures. Includes also references to points of interest. This layer is part of a selection of digitally scanned and georeferenced historic maps of New England from the Harvard Map Collection. These maps typically portray both natural and manmade features. The selection represents a range of regions, originators, ground condition dates, scales, and map purposes.

Philadelphia, Pennsylvania and Camden, New Jersey, 1886 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Plan of the city of Philadelphia and Camden, drawn and engraved by W.H. Gamble. It was published by Wm. M. Bradley & Bro. in 1886. Scale [ca.1:25,000]. The image inside the map neatline is georeferenced to the surface of the earth and fit to the Pennsylvania South State Plane Coordinate System NAD83 (in Feet) (Fipszone 3702). All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map. This map shows features such as roads, railroads, drainage, selected public buildings, city wards, parks, cemeteries, ferry routes, wharves, and more. This layer is part of a selection of digitally scanned and georeferenced historic maps from The Harvard Map Collection as part of the Imaging the Urban Environment project. Maps selected for this project represent major urban areas and cities of the world, at various time periods. These maps typically portray both natural and manmade features at a large scale. The selection represents a range of regions, originators, ground condition dates, scales, and purposes.

Philadelphia, Pennsylvania, 1882 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: New map of Philadelphia. It was published by Pickwick & Co., Booksellers in 1882. Scale not given. Covers also a portion of Camden, New Jersey. The image inside the map neatline is georeferenced to the surface of the earth and fit to the Pennsylvania South State Plane Coordinate System NAD83 (in Feet) (Fipszone 3702). All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map. This map shows features such as roads, railroads, drainage, selected public buildings, city wards, parks, cemeteries, wharves, ferry routes, and more. This layer is part of a selection of digitally scanned and georeferenced historic maps from The Harvard Map Collection as part of the Imaging the Urban Environment project. Maps selected for this project represent major urban areas and cities of the world, at various time periods. These maps typically portray both natural and manmade features at a large scale. The selection represents a range of regions, originators, ground condition dates, scales, and purposes.

Philadelphia, Pennsylvania, 1893 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: New map of the city of Philadelphia :from the latest city surveys : prepared for Gopsill's directories 1893. It was published by J.L. Smith in 1893. Scale [ca.1:21,500]. Covers Philadelphia and a portion of surrounding cities. The image inside the map neatline is georeferenced to the surface of the earth and fit to the Pennsylvania South State Plane Coordinate System NAD83 (in Feet) (Fipszone 3702). All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map. This map shows features such as roads, railroads, drainage, selected public buildings, cemeteries, parks, city wards, and more. Includes three indices: Street directory -- Statistical notes -- Elevation of the highest recorded points above high tides in the Delaware River. This layer is part of a selection of digitally scanned and georeferenced historic maps from The Harvard Map Collection as part of the Imaging the Urban Environment project. Maps selected for this project represent major urban areas and cities of the world, at various time periods. These maps typically portray both natural and manmade features at a large scale. The selection represents a range of regions, originators, ground condition dates, scales, and purposes.

Philadelphia, Pennsylvania, 1900 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: New map of the city of Philadelphia, 1900 : from the latest city surveys : prepared for Gopsill's directories 1900. It was published by J. L. Smith in 1900. Scale [ca. 1:21,500]. Covers Philadelphia and a portion of surrounding cities. The image inside the map neatline is georeferenced to the surface of the earth and fit to the Pennsylvania South State Plane Coordinate System NAD83 (in Feet) (Fipszone 3702). All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map. This map shows features such as roads, railroads, drainage, canals, city wards, parks, cemeteries, wharves, selected public buildings, and more. Includes street directory, statistical notes, and list of elevations. This layer is part of a selection of digitally scanned and georeferenced historic maps from The Harvard Map Collection as part of the Imaging the Urban Environment project. Maps selected for this project represent major urban areas and cities of the world, at various time periods. These maps typically portray both natural and manmade features at a large scale. The selection represents a range of regions, originators, ground condition dates, scales, and purposes.

Philadelphia, Pennsylvania, Camden, New Jersey and vicinity, 1921 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Map of Philadelphia, Camden and vicinity : compiled from city plans & personal surveys, engraved by Albert Volk. It was published by Elvino V. Smith in 1921. Scale 1:35,000. The image inside the map neatline is georeferenced to the surface of the earth and fit to the Pennsylvania South State Plane Coordinate System NAD83 (in Feet) (Fipszone 3702). All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map. This map shows features such as roads, railroads, drainage, county, township, and city ward boundaries, parks, cemeteries, and more. This layer is part of a selection of digitally scanned and georeferenced historic maps from The Harvard Map Collection as part of the Imaging the Urban Environment project. Maps selected for this project represent major urban areas and cities of the world, at various time periods. These maps typically portray both natural and manmade features at a large scale. The selection represents a range of regions, originators, ground condition dates, scales, and purposes.