Specific recruitment of SH-PTP1 to the erythropoietin receptor causes inactivation of JAK2 and termination of proliferative signals

Article Abstract:

A study of the mechanism of inactivation of protein tyrosine kinase JAK2 reveals that the inactivation occurs through the binding of the hematopoietic protein tyrosine phosphatase SH-PTP1 to the tyrosine-phosphorylated erythropoietin receptor EPO-R through its SH2 domains. In vitro studies indicate the Y429 in the cytoplasmic region of EPO-R is the SH-PTP1 binding site. The ability to bind SH-PTP1 is absent in mutant EPO-Rs that lack Y429. Mutant cells exhibit sustained autophosphorylation of JAK2 activated by EPO as they are highly sensitive to EPO.

Physiological aspects, Protein tyrosine kinase, Protein-tyrosine kinase, Phosphorylation, Erythropoietin

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SH2 domains recognize specific phosphopeptide sequences

Article Abstract:

The sequence specificity of the peptide-binding sites of Src homology 2 (SH2) domains was examined using a phosphopeptide library. SH2 domains provide phosphorylation-dependent and sequence-specific contacts for the assembly of receptor signaling complexes, which are essential in cellular signal transduction. The results revealed two SH2 domain groups based on preference for two general peptide sequence motifs. Other features of selectivity for certain peptide sequences were observed, suggesting a structural basis for selectivity in SH2 binding.

Cellular signal transduction, Amino acid sequence, Amino acid sequencing

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The structural basis for 14-3-3: Phosphopeptide binding specificity

Article Abstract:

14-3-3 proteins mediate signal transduction by binding to proteins containing phosphoserine. RSXpSXP and RXY/FXpSXP, binding motifs, have been identified as being present in most known 14-3-3 binding proteins. The crystal structure of 14-3-3zeta was complexed with a phosphoserine motif in polyoma middle-T, and determined to 2.6 A resolution. It is shown that the 14-3-3 dimer tightly binds to single molecules, reflecting bidentate association as a signaling mechanism.

Observations, Transduction, Transduction (Genetics)

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