Structurally distinct phosphatases CD45 and CD148 both regulate B cell and macrophage immunoreceptor signaling

Area of Science:

• Immunology
• Cell Biology
• Biochemistry

Background:

• Receptor-type protein tyrosine phosphatase (RPTP) CD148 is primarily known for inhibiting signaling and proliferation in nonhematopoietic cells.
• The specific functions of CD148 within the immune system, particularly in lymphocytes and myeloid cells, remain largely uncharacterized.

Purpose of the Study:

• To investigate the role of CD148 in immune cell regulation.
• To elucidate the relationship between CD148 and CD45 in B cell and macrophage function and development.

Main Methods:

• Analysis of CD148 loss-of-function mouse models.
• Comparative study of CD148 and CD45 doubly deficient B cells and macrophages.
• Assessment of Src family kinase (SFK) phosphorylation status.

Main Results:

• CD148 exhibits a positive regulatory function in B cells and macrophages, analogous to CD45's role in Src family kinases (SFKs).
• Double deficiency of CD148 and CD45 in B and myeloid cells leads to hyperphosphorylation of SFKs' C-terminal inhibitory tyrosine.
• Significant alterations in B and myeloid lineage development and impaired immunoreceptor signaling were observed in doubly deficient cells.

Conclusions:

• The C-terminal tyrosine of SFKs is a common substrate for both CD148 and CD45 phosphatases.
• A previously unrecognized functional redundancy exists between CD148 and CD45 in regulating immune cell signaling and development.
• Re-evaluation of CD45's function in B and myeloid lineages is necessary, considering the implications of CD148's overlapping role.