Shb and Its Homologues: Signaling in T Lymphocytes and Fibroblasts [Elektronisk resurs]

• Stimulation of the T cell receptor (TCR) induces tyrosine phosphorylation of numerous intracellular proteins, leading to activation of the interleukin-2 (IL-2) gene in T lymphocytes. Shb is a ubiquitously expressed adapter protein, with the ability to associate with the T cell receptor and several signaling proteins in T cells, including: the TCR ζ-chain, LAT, PLC-γ1, Vav, SLP-76 and Gads. Jurkat T cells expressing Shb with a mutation in the SH2 domain, exhibited reduced phosphorylation of several proteins and abolished activation of the MAP kinases ERK1, ERK2 and JNK, upon CD3 stimulation. The TCR induced Ca 2+ response in these cells was abolished, together with the activation of the IL-2 promoter via the transcription factor NFAT. Consequently, IL-2 production was also perturbed in these cells, compared to normal Jurkat T cells. Shb was also seen to associate with the β and γ chains of the IL-2 receptor, upon IL-2 stimulation, in T and NK cells. This association occurred between the Shb SH2 domain and Tyr-510 of the IL-2R β chain. The proline-rich domains of Shb were found to associate with the tyrosine kinases JAK1 and JAK3, which are important for STAT-mediated proliferation of T and NK cells upon IL-2 stimulation. Shb was also found to be involved in IL-2 mediated regulation of apoptosis. These findings indicate a dual role for Shb in T cells, where Shb is involved in both T cell receptor and IL-2 receptor signaling. A Shb homologue, Shf was identified, and seen to associate with the PDGF-α-receptor. Shf shares high sequence homology with Shb and a Shd (also of the Shb family) in the SH2 domain and in four motifs containing putative tyrosine phosphorylation sites. When Shf was overexpressed in fibroblasts, these cells displayed significantly lower rates of apoptosis than control cells in the presence of PDGF-AA. These findings suggest a role for the novel adapter Shf in PDGF-receptor signaling and regulation of apoptosis. 

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Medical and Health Sciences  (hsv)

Basic Medicine  (hsv)

Cell and Molecular Biology  (hsv)

Medicin och hälsovetenskap  (hsv)

Medicinska och farmaceutiska grundvetenskaper  (hsv)

Cell- och molekylärbiologi  (hsv)

MEDICINE  (svep)

Morphology, cell biology, pathology  (svep)

Cell biology  (svep)

MEDICIN  (svep)

Morfologi, cellbiologi, patologi  (svep)

Cellbiologi  (svep)

medicinsk cellbiologi  (uu)

Medical Cell Biology  (uu)

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government publication  (marcgt)

Indexterm och SAB-rubrik

Cell biology

Shb

T cell receptor

IL-2 receptor

PDGF receptor

cell signaling

adapter proteins

LAT

Vav

PLC-g1

SLP-76

JAK1

JAK3

Jurkat cells

T cells

NK cells

Apoptosis.

Cellbiologi