University of Massachusetts

Jes K Klarlund

Michael P Czech

The present invention relates to the discovery of a novel isoform of phosphatidylinositide binding protein, referred to herein a &ldquo;general receptors for phosphoinositides&rdquo; or &ldquo;GRPs&rdquo;. The GRP molecules show a modular structure comprising a domain homologous to the yeast SEC7 gene product and a pleckstrin homology (PH) domain. GRP proteins exhibit specific high affinity binding to products of the lipid kinase phosphatidylinositol-3-OH kinase, such as phosphotidylinositol-3,4,5. As described herein, GRP proteins may function as adaptors between membrane signalling and multiple downstream targets. Thus, GRP polypeptides potentially mediate multiple signalling events such as cell adhesion and membrane trafficking, among others. This invention describes isolated and antisense nucleic acids molecules, recombinant expression vectors containing a nucleic acid molecule of the invention, host cells into which the expression vectors have been introduced and non-human transgenic animals in which GRP gene has been introduced or disrupted. In addition, the invention provides isolated GRP proteins, fusion proteins, antigenic peptides and anti-GRP antibodies. Diagnostic, screening and therapeutic methods utilizing compositions of the invention are also provided. The invention further provides a method of cloning novel phosphatidylinositol binding protein.

General receptors for phosphoinositides and uses related thereto

Novel phosphatidylinositide binding proteins, referred to herein a &ldquo;general receptors for phosphoinositides&rdquo; or &ldquo;GRPs&rdquo; are disclosed which are useful as adaptors between membrane signalling and multiple downstream targets. This invention describes isolated and antisense nucleic acids molecules, recombinant expression vectors containing a nucleic acid molecule of the invention, host cells into which the expression vectors have been introduced and non-human transgenic animals in which GRP gene has been introduced or disrupted. In addition, the invention provides isolated GRP proteins, fusion proteins, antigenic peptides and anti-GRP antibodies. Diagnostic, screening and therapeutic methods utilizing compositions of the invention are also provided. The invention further provides a method of cloning novel phosphatidylinositol binding proteins.

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Worcester, MA, United States of America

Jes K Klarlund