The protein tyrosine phosphatase SHP-1 regulates integrin-mediated adhesion of macrophages. 1998

T I Roach, and S E Slater, and L S White, and X Zhang, and P W Majerus, and E J Brown, and M L Thomas
Department of Pathology, Howard Hughes Medical Institute, Washington University School of Medicine, St Louis, Missouri 63130, USA.

The Src homology 2 domain phosphatase-1 (SHP-1) is a tyrosine phosphatase containing two amino-terminal SH2 domains and is expressed primarily by hematopoietic-derived cells [1]. The viable motheaten (Hcphme-v) mutant mice (mev) suffer from progressive inflammation due to a deficiency of SHP-1 enzyme activity [2,3] and die at 3-4 months of age from macrophage and neutrophil accumulation in the lung [4]. The mechanism by which SHP-1 deficiency leads to inflammation is unknown. We found that macrophages from mev mice adhered and spread to a greater extent than normal macrophages through alpha m beta 2 integrin-mediated contacts. Whereas macrophages deficient in the transmembrane tyrosine phosphatase CD45 (CD45-/-) spontaneously detached from alpha m beta 2 integrin contacts [5], cells deficient in both CD45 and SHP-1 did not. In SHP-1 deficient macrophages there was a 10-15-fold increase in D-3 phospholipid products of phosphatidylinositol (PI) 3-kinase. Concomitantly, there was a 2-5-fold increase in membrane-associated PI 3-kinase activity in mev macrophages relative to normal macrophages. Treatment of macrophages with the PI 3-kinase inhibitors wortmannin or LY294002 resulted in a dramatic detachment of cells, indicating that PI 3-kinase activity is required for adhesion. These data demonstrate that SHP-1 is necessary for detachment from alpha m beta 2 integrin-mediated contacts in primary macrophages and suggest that a defect in this pathway may contribute to inflammatory disease.

UI MeSH Term Description Entries
D007249 Inflammation A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. Innate Inflammatory Response,Inflammations,Inflammatory Response, Innate,Innate Inflammatory Responses
D008264 Macrophages The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.) Bone Marrow-Derived Macrophages,Monocyte-Derived Macrophages,Macrophage,Macrophages, Monocyte-Derived,Bone Marrow Derived Macrophages,Bone Marrow-Derived Macrophage,Macrophage, Bone Marrow-Derived,Macrophage, Monocyte-Derived,Macrophages, Bone Marrow-Derived,Macrophages, Monocyte Derived,Monocyte Derived Macrophages,Monocyte-Derived Macrophage
D008817 Mice, Mutant Strains Mice bearing mutant genes which are phenotypically expressed in the animals. Mouse, Mutant Strain,Mutant Mouse Strain,Mutant Strain of Mouse,Mutant Strains of Mice,Mice Mutant Strain,Mice Mutant Strains,Mouse Mutant Strain,Mouse Mutant Strains,Mouse Strain, Mutant,Mouse Strains, Mutant,Mutant Mouse Strains,Mutant Strain Mouse,Mutant Strains Mice,Strain Mouse, Mutant,Strain, Mutant Mouse,Strains Mice, Mutant,Strains, Mutant Mouse
D001854 Bone Marrow Cells Cells contained in the bone marrow including fat cells (see ADIPOCYTES); STROMAL CELLS; MEGAKARYOCYTES; and the immediate precursors of most blood cells. Bone Marrow Cell,Cell, Bone Marrow,Cells, Bone Marrow,Marrow Cell, Bone,Marrow Cells, Bone
D002448 Cell Adhesion Adherence of cells to surfaces or to other cells. Adhesion, Cell,Adhesions, Cell,Cell Adhesions
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D016023 Integrins A family of transmembrane glycoproteins (MEMBRANE GLYCOPROTEINS) consisting of noncovalent heterodimers. They interact with a wide variety of ligands including EXTRACELLULAR MATRIX PROTEINS; COMPLEMENT, and other cells, while their intracellular domains interact with the CYTOSKELETON. The integrins consist of at least three identified families: the cytoadhesin receptors (RECEPTORS, CYTOADHESIN), the leukocyte adhesion receptors (RECEPTORS, LEUKOCYTE ADHESION), and the VERY LATE ANTIGEN RECEPTORS. Each family contains a common beta-subunit (INTEGRIN BETA CHAINS) combined with one or more distinct alpha-subunits (INTEGRIN ALPHA CHAINS). These receptors participate in cell-matrix and cell-cell adhesion in many physiologically important processes, including embryological development; HEMOSTASIS; THROMBOSIS; WOUND HEALING; immune and nonimmune defense mechanisms; and oncogenic transformation. Integrin
D017027 Protein Tyrosine Phosphatases An enzyme group that specifically dephosphorylates phosphotyrosyl residues in selected proteins. Together with PROTEIN-TYROSINE KINASE, it regulates tyrosine phosphorylation and dephosphorylation in cellular signal transduction and may play a role in cell growth control and carcinogenesis. Phosphotyrosine Phosphatase,Protein-Tyrosine-Phosphatase,Tyrosyl Phosphoprotein Phosphatase,PTPase,Phosphotyrosyl Protein Phosphatase,Protein-Tyrosine Phosphatase,Phosphatase, Phosphotyrosine,Phosphatase, Phosphotyrosyl Protein,Phosphatase, Protein-Tyrosine,Phosphatase, Tyrosyl Phosphoprotein,Phosphatases, Protein Tyrosine,Phosphoprotein Phosphatase, Tyrosyl,Protein Phosphatase, Phosphotyrosyl,Protein Tyrosine Phosphatase,Tyrosine Phosphatases, Protein
D017493 Leukocyte Common Antigens High-molecular weight glycoproteins uniquely expressed on the surface of LEUKOCYTES and their hemopoietic progenitors. They contain two FIBRONECTIN TYPE III DOMAINS and possess cytoplasmic protein tyrosine phosphatase activity, which plays a role in intracellular signaling from the CELL SURFACE RECEPTORS. Leukocyte common antigens occur as multiple isoforms that result from alternative mRNA splicing and differential usage of three exons. Antigens, CD45,CD45 Antigens,CD45R Antigens,CD45RA Antigens,CD45RO Antigens,Protein Tyrosine Phosphatase, Receptor Type, C,2H4 Antigens,B220 Antigen,B220 Antigens,CD45 Antigen,CD45R0 Antigens,CD45RB Antigens,CD45RCAntigens,L-CA Antigens,Leukocyte Common Antigen,T200 Antigens,Antigen, B220,Antigen, CD45,Antigen, Leukocyte Common,Antigens, 2H4,Antigens, B220,Antigens, CD45R,Antigens, CD45R0,Antigens, CD45RA,Antigens, CD45RB,Antigens, CD45RO,Antigens, L-CA,Antigens, Leukocyte Common,Antigens, T200,L CA Antigens
D047908 Intracellular Signaling Peptides and Proteins Proteins and peptides that are involved in SIGNAL TRANSDUCTION within the cell. Included here are peptides and proteins that regulate the activity of TRANSCRIPTION FACTORS and cellular processes in response to signals from CELL SURFACE RECEPTORS. Intracellular signaling peptide and proteins may be part of an enzymatic signaling cascade or act through binding to and modifying the action of other signaling factors. Intracellular Signaling Peptides,Intracellular Signaling Proteins,Peptides, Intracellular Signaling,Proteins, Intracellular Signaling,Signaling Peptides, Intracellular,Signaling Proteins, Intracellular

Related Publications

T I Roach, and S E Slater, and L S White, and X Zhang, and P W Majerus, and E J Brown, and M L Thomas
September 2012, Journal of immunology (Baltimore, Md. : 1950),
T I Roach, and S E Slater, and L S White, and X Zhang, and P W Majerus, and E J Brown, and M L Thomas
August 1998, The Journal of biological chemistry,
T I Roach, and S E Slater, and L S White, and X Zhang, and P W Majerus, and E J Brown, and M L Thomas
June 2004, The Journal of biological chemistry,
T I Roach, and S E Slater, and L S White, and X Zhang, and P W Majerus, and E J Brown, and M L Thomas
November 2000, Current biology : CB,
T I Roach, and S E Slater, and L S White, and X Zhang, and P W Majerus, and E J Brown, and M L Thomas
December 1997, The Journal of biological chemistry,
T I Roach, and S E Slater, and L S White, and X Zhang, and P W Majerus, and E J Brown, and M L Thomas
May 1999, Journal of immunology (Baltimore, Md. : 1950),
T I Roach, and S E Slater, and L S White, and X Zhang, and P W Majerus, and E J Brown, and M L Thomas
July 2003, The Journal of biological chemistry,
T I Roach, and S E Slater, and L S White, and X Zhang, and P W Majerus, and E J Brown, and M L Thomas
May 1999, Journal of immunology (Baltimore, Md. : 1950),
T I Roach, and S E Slater, and L S White, and X Zhang, and P W Majerus, and E J Brown, and M L Thomas
June 1999, Journal of immunology (Baltimore, Md. : 1950),
T I Roach, and S E Slater, and L S White, and X Zhang, and P W Majerus, and E J Brown, and M L Thomas
January 1998, Current biology : CB,
Copied contents to your clipboard!