Lck-dependent tyrosyl phosphorylation of the phosphotyrosine phosphatase SH-PTP1 in murine T cells.
The phosphorylation and dephosphorylation of proteins on tyrosyl residues are key regulatory mechanisms in T-cell signal transduction and are controlled by the opposing activities of protein tyrosine kinases and phosphotyrosyl phosphatases (PTPs). In T cells, several nontransmembrane protein tyrosine kinases are associated with receptors; for example, Lck is bound to ... the coreceptors CD4 and CD8 and becomes activated upon their stimulation. In comparison, little is known about the role of nontransmembrane PTPs in early T-cell signaling. SH-PTP1 (PTP1C, HCP, SHP) is a nontransmembrane PTP expressed primarily in hematopoietic cells, including T cells. We have found that SH-PTP1 is basally phosphorylated on serine in resting T cells. Upon stimulation of CD4 or CD8 either in a T-cell hybridoma cell line or in primary thymocytes, SH-PTP1 becomes tyrosyl phosphorylated. Moreover, SH-PTP1 is constitutively phosphorylated on tyrosine in the Lck-overexpressing lymphoma cell line LSTRA. SH-PTP1 is also a good substrate for recombinant Lck in vitro. Comparisons of the tryptic phosphopeptide maps of wild-type SH-PTP1 and deletion and point mutations establish that the two sites (Y-536 and Y-564) which are directly phosphorylated by Lck in vitro are also phosphorylated in vivo in LSTRA cells. One of these sites (Y-564) is phosphorylated in T cells in response to Lck activation. We conclude that SH-PTP1 undergoes Lck-dependent tyrosyl phosphorylation in T cells and likely plays a role in early T-cell signaling.
Mesh Terms:
Amino Acid Sequence, Animals, Antigens, CD4, Antigens, CD8, Base Sequence, DNA Primers, Humans, Lymphocyte Activation, Lymphocyte Specific Protein Tyrosine Kinase p56(lck), Mice, Molecular Sequence Data, Peptide Mapping, Phosphorylation, Protein Tyrosine Phosphatases, Protein-Tyrosine Kinases, Receptors, Immunologic, Recombinant Proteins, Signal Transduction, T-Lymphocytes
Amino Acid Sequence, Animals, Antigens, CD4, Antigens, CD8, Base Sequence, DNA Primers, Humans, Lymphocyte Activation, Lymphocyte Specific Protein Tyrosine Kinase p56(lck), Mice, Molecular Sequence Data, Peptide Mapping, Phosphorylation, Protein Tyrosine Phosphatases, Protein-Tyrosine Kinases, Receptors, Immunologic, Recombinant Proteins, Signal Transduction, T-Lymphocytes
Mol. Cell. Biol.
Date: Mar. 01, 1994
PubMed ID: 8114715
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