Rapid degradation of protein tyrosine phosphatase 1B in sickle cells: Possible contribution to sickle cell membrane weakening

Although both protein tyrosine phosphatases and kinases are constitutively active in healthy human red blood cells (RBCs), the preponderance of phosphatase activities maintains the membrane proteins in a predominantly unphosphorylated state. We report here that unlike healthy RBCs, proteins in sickl...

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Bibliographic Details
Published in:The FASEB journal 2022-06, Vol.36 (6), p.e22360-n/a
Main Authors: Noomuna, Panae, Hausman, John M., Sansoya, Ruhani, Kalfa, Theodosia, Risinger, Mary, Low, Philip S.
Format: Article
Language:English
Subjects:
Anemia, Sickle Cell - metabolism
Band 3 tyrosine phosphorylation
calpain proteolysis
cleavage of PTP1B
Erythrocyte Membrane - metabolism
Humans
Membrane Proteins - metabolism
phosphatase activity
Phosphorylation
Protein Tyrosine Phosphatase, Non-Receptor Type 1 - genetics
Protein Tyrosine Phosphatase, Non-Receptor Type 1 - metabolism
PTP1B
sickle cells
Tyrosine - metabolism
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Summary:Although both protein tyrosine phosphatases and kinases are constitutively active in healthy human red blood cells (RBCs), the preponderance of phosphatase activities maintains the membrane proteins in a predominantly unphosphorylated state. We report here that unlike healthy RBCs, proteins in sickle cells are heavily tyrosine phosphorylated, raising the question regarding the mechanism underpinning this tyrosine phosphorylation. Upon investigating possible causes, we observe that protein tyrosine phosphatase 1B (PTP1B), the major erythrocyte tyrosine phosphatase, is largely digested to a lower molecular weight fragment in sickle cells. We further find that the resulting truncated form of PTP1B is significantly less active than its intact counterpart, probably accounting for the intense tyrosine phosphorylation of Band 3 in sickle erythrocytes. Because this tyrosine phosphorylation of Band 3 promotes erythrocyte membrane weakening that causes release of both membrane vesicles and cell free hemoglobin that in turn initiates vaso‐occlusive events, we conclude that cleavage of PTP1B could contribute to the symptoms of sickle cell disease. We further posit that methods to inhibit proteolysis of PTP1B could mitigate symptoms of the disease.
ISSN:0892-6638
1530-6860
DOI:10.1096/fj.202100809RR