Accession Number : ADA300403

Title :   Role of SHPTP2 in Mitogenic Signaling.

Descriptive Note : Annual rept. 30 Sep 94-29 Sep 95,

Corporate Author : IOWA UNIV IOWA CITY

Personal Author(s) : Pessin, Jeffrey E.

PDF Url : ADA300403

Report Date : 04 AUG 1995

Pagination or Media Count : 24

Abstract : During the past funding period, we have made excellent progress in our overall objectives to determine the signaling mechanisms of the protein tyrosine-specific phosphatase, SHPTP2. These current studies have resulted in our demonstration that SHPTP2 is a required positive effector in mediating both insulin and EGF receptor signaling events leading to the activation of ras mid the ERK pathway. Since, activation of the ras/raf/MEK/ERK pathway is sufficient for mitogenesis, these data demonstrate that SHPTP2 is an important upstream mediator for growth factor stimulated mitogenesis. In order to identify the specific associated proteins and/or direct substrates for SHPTP2 activity, we have successfully performed a series of co-immunoprecipitation studies with carboxyl terminal SHPTP2 antibodies. These studies have identified a novel 115 kDa protein that is tyrosine phosphorylated and associated with SHPTP2 following insulin and BGF stimulation but not PDGF. This pp115 protein is the predominant SHPTP2 binding protein which appears to function both as a substrate as well as a docking protein based upon expression studies using a mutant SHPTP2 in which the catalytic cysteine was replaced with a serine residue. During the next bu get period, we will be attempting to purify and further characterize this pp115 protein in order to determine its function as an upstream activator of ras.

Descriptors :   *PHOSPHATES, *TYROSINE, ACTIVATION, STIMULATION(GENERAL), PROTEINS, SUBSTRATES, PRECIPITATION, ANTIBODIES, CATALYSIS, IMMUNOASSAY, CYSTEINE, SENSE ORGANS, INSULIN, SERINE.

Subject Categories : Inorganic Chemistry

Distribution Statement : APPROVED FOR PUBLIC RELEASE