Abstracts (complete list) - Wissenschaft Online

Mandy Pierau, Engelmann Swen, Thomas Drewes, Thabo Lapp, Dirk Reinhold,
Burkhart Schraven, Ursula Bommhardt
Cross-talk between PKB/Akt and TGFβ signalling in T cell
activation
The TGFβ family of cytokines are important regulators of cellular proliferation, apoptosis
and differentiation. TGFβ is a key regulator of inflammatory responses and has been
linked to the pathogenesis of experimental autoimmune encephalomyelitis (EAE).
Binding of TGFβ to type II and type I serine-threonine kinase receptors leads to
phosphorylation of the intracellular signal mediators, the Smad proteins. Activated
Smad2 and Smad3 bind Smad4 and as heteromeric Smad complexes, once translocated
to the nucleus, cooperate with other nuclear co-factors to induce the transcription of
target genes. Several Smad regulatory proteins control the subcellular localization,
phosphorylation and the binding of transcriptional partners of the Smads. Interestingly,
a cross-talk between TGFβ signalling and the PI3K/PDK1/PKB pathway has been
suggested from findings in cell lines that Smad proteins can physically interact with PKB
or PDK1. We previously showed that T cells from transgenic (tg) mice expressing a
constitutively active form of PKBα (myrPKB) are hyperreactive and show enhanced
survival. Surprisingly, MOG-peptide induced EAE in myrPKB tg mice showed a milder
disease progression compared to wild type mice. Since the amelioration of EAE
pathology in myrPKB tg mice could be coupled to differences in TGFβ-mediated
signalling events, we studied the response of T cells to TGFβ. In contrast to wild type
CD4+ T cells TCR/CD3 induced proliferation of myrPKB tg T cells proceeded in the
presence of TGFβ. Active PKB thus counteracts the inhibitory signals of TGFβ, although
nuclear translocation of activated Smad2/3 proteins was normal. Data on candidate
proteins that are affected by myrPKB and likely contribute to the "resistance" to TGFβ
will be presented and discussed.