Year: 2001
Type: dissertation
Abstract: While an important role for the PTEN phosphatase in the modulation of TCR signaling is suggested by many lines of evidence, little is known about the biochemical mechanisms whereby PTEN impacts on TCR function. To address this issue, affinity chromatography and mass spectrometry were used to isolate and identify T cell proteins representing binding-partners for PTEN. This approach led to the identification of seven potential PTEN ligands including the SET, PHAPI2b, PHAPI, tubulin beta-1, eta and theta subunits of chaperonin containing T-complex protein 1, nucleolin and moesin proteins, with apparent molecular weights of 23, 28, 30, 50, 55, 67 and 67 kDa, respectively. An analysis of PTEN roles in T cell activation was also undertaken and the results revealed PTEN to be inducibly tyrosine phosphorylated consequent to cross-linking of the T cell antigen and CD28 receptors. AKT phosphorylation was also observed following TCR/CD28 costimulation and was found to be relatively increased in thymocytes lacking the SHP-1 tyrosine phosphatase. These results suggest that the PI3K/AKT signaling cascade plays a role in TCR-elicited T cell activation and that this pathway is regulated by SHP-1. As PTEN plays a critical role in downregulation the coupling of TCR engagement to AKT phosphorylation/activation, these results raise the possibility that dephosphorylation of PTEN represents a mechanism whereby SHP-1 inhibits TCR signaling.
Author: Karen Andrea Berg
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2885571647