Accession Number : ADA336684

Title :   Role of SHPTP2 in Mitogenic Signaling.

Descriptive Note : Final rept 30 Sep 94-31 Aug 97.

Corporate Author : IOWA UNIV IOWA CITY

Personal Author(s) : Pessin, Jeffrey E.

PDF Url : ADA336684

Report Date : SEP 1997

Pagination or Media Count : 15

Abstract : As indicated in our previous progress report, our initial objectives were to determine the role of SHPTP2 in the growth factor (insulin and epidermal growth factor) activation of Ras. However, these studies have lead us to uncover several novel pathways that together coordinately regulate Ras-dependent downstream signaling of the Raf/MEK/ERK cascade. Initially, we defined a feedback pathway which resulted in the serine/threonine phosphorylation of SOS and which was responsible, at least in part, for the termination of Ras activation. Currently, we are in the process of identifying the sites of phosphorylation responsible for the dissociation of Grb2 from SOS. During the past funding period, we have observed that another small GTP binding protein, termed Rap1, functions as a negative regulator of Ras by inhibiting the activation of the Raf/MEK/ERK cascade. However, growth factor stimulation decompresses this inhibition by converting active Rap1 to inactive Rap1. This occurs concomitant with the activation of Ras leading to a net activation of Raf/MEK/ERK pathway. In addition, our preliminary data suggests that the inhibition of Rap1 results from a rapid dissociation of the CrkII-C3G complex due to the direct tyrosine phosphorylation of CrkII.

Descriptors :   *EPIDERMIS, *INSULIN, *TYROSINE, ACTIVATION, STIMULATION(PHYSIOLOGY), CLINICAL MEDICINE, NEOPLASMS, REGULATORS, CHEMICAL BONDS, MEDICAL SERVICES, INHIBITION, CELLS(BIOLOGY), DISSOCIATION, RECEPTOR SITES(PHYSIOLOGY), AMINO ACIDS, CANCER, GROWTH(PHYSIOLOGY), SERINE, PHOSPHORYLATION, BREAST CANCER.

Subject Categories : Pharmacology

Distribution Statement : APPROVED FOR PUBLIC RELEASE