Harvard College

Children's Medical Center Corporation

Oxford University Innovation Limited

John G Flanagan

Philip Leder

Hwai-Jong Cheng

Michael Klagsbrun

Edith Yvonne Jones

David M Ornitz

Avner Yayon

Alexandru Radu Aricescu

Edna E Sun

Charlotte Hannah Coles

Ming-Ko Chiang

Yingjie Shen

Qiang Lu

Disclosed herein are methods of inducing neuronal outgrowth of a neuron. The methods comprise contacting the neuron with an agent that binds receptor protein tyrosine phosphatase &#x3b4; (RPTP&#x3b4;), to thereby induce neuronal outgrowth of the neuron. The agent may induces clustering of RPTP&#x3b4; and/or inhibit binding of chondroitin sulfate proteoglycan (CSPG) to RPTP&#x3b4;. Examples of suitable agents are heparan sulfate proteoglycan, heparan sulfate, heparan sulfate oligosaccharides, or heparin oligosaccharides. Additional agents are also disclosed. The neuron can be a CNS neuron or peripheral neuron. Also disclosed herein are methods of treating neuronal injury in a subject comprising, administering to the subject an agent that binds RPTP&#x3b4;. Administration may be to a site of neuronal injury, to thereby induce neuronal outgrowth at the site of neuronal injury.

Methods of promoting neuronal outgrowth by gypican 2 that binds to receptor protein tyrosine phosphatase sigma

Transmembrane B ephrins and their Eph receptors signal hi-directionally. The presently claimed invention describes a cytoplasmic protein, designated PDZ-RGS3, which binds B ephrins through a PDZ domain, and has a regulator of heterotrimeric G protein signaling (RGS) domain. PDZ-RGS3 mediates signaling from the ephrin-B cytoplasmic tail. SDF-1, a chemokine with a G protein coupled receptor, or BDNF, act as chemoattractants for cerebellar granule cells, with SDF-1 action being selectively inhibited by soluble EphB receptor. The claimed invention reveals a pathway that links reverse signaling to cellular guidance, uncovers a novel mode of control for G proteins, and demonstrates a mechanism for selective regulation of responsiveness to neuronal guidance cues. Further, compositions and methods of use are provided for modulating cell migration as a function of chemokines and GPCR interaction, to aid in the treatment of disease states and medical conditions, including cancer and immune responses such as allergy and autoimmune responses. In one embodiment, a method of altering the sensitivity of a cell to a chemokine is provided using a PDZ-RGS3 protein.

Protein waving a PDZ and a RGS domain

The present invention relates to the discovery of a novel EPH receptor ligand, referred to hereinafter as &ldquo;Elf-1&rdquo;, which protein has apparently broad involvement in the formation and maintenance of ordered spatial arrangements of differentiated tissues in vertebrates, and can be used to generate and/or maintain an array of different vertebrate tissue both in vitro and in vivo.

EPH receptor ligands, and uses related thereto

We describe here a new class of protein tyrosine phosphatases (PTP), called &ldquo;PTP-NP&rdquo; (for neural and pancreatic) receptors. The sequence of an exemplary PTP-NP gene (SEQ ID No. 1) indicates it encodes a receptor type PTP (SEQ ID No. 2) with a single tyrosine phosphatase domain. Comparison of PTP-NP with the other known PTPs reveals a cysteine-conserved motif in the extracellular domain and, together with their homology in the phosphatase domain, this defines a new subclass of receptor type PTPs.

Nucleic acids encoding neural/pancreatic receptor tyrosine phosphatase

Disclosed is a method of isolating a ligand from a sample, the method including: providing a hybrid molecule including the receptor for the ligand covalently bonded to the first member of a specific binding pair; contacting sample with the hybrid molecule to form an affinity complex between the ligand and the hybrid molecule; and isolating the affinity complex using the second member of the specific binding pair. Also disclosed is a c-kit ligand, nucleic acid encoding such a ligand, and recombinant cells containing such nucleic acid. The c-kit ligand may be used to stimulate hematopoietic cell growth.

Detection and isolation of receptors

The present invention relates to the discovery of a novel EPH receptor ligand, referred to hereinafter as 'Elf-1', which protein has apparently broad involvement in the formation and maintenance of ordered spatial arrangements of differentiated tissues in vertebrates, and can be used to generate and/or maintain an array of different vertebrate tissue both in vitro and in vivo.

A homogeneous population of cells having on average (1) a number of cell surface low-affinity heparin-binding growth factor (HBGF) sites per cell less than 20% of the number of such binding sites found on wild-type CHO-K1 cells (ATCC Accession No. CCL61), and at least three times the number of cell surface high-affinity HBGF receptors per cell found on such CHO-K1 cells; and an assay system utilizing such cells.

Growing community of inventors

Newton, MA, United States of America

John G Flanagan