Final published version
Research output: Contribution to Journal/Magazine › Review article › peer-review
Research output: Contribution to Journal/Magazine › Review article › peer-review
}
TY - JOUR
T1 - Modulation of immune cell signalling by the leukocyte common tyrosine phosphatase, CD45
AU - Saunders, A E
AU - Johnson, P
PY - 2010/3/31
Y1 - 2010/3/31
N2 - CD45 is a leukocyte specific transmembrane glycoprotein and a receptor-like protein tyrosine phosphatase (PTP). CD45 can be expressed as several alternatively spliced isoforms that differ in the extracellular domain. The isoforms are regulated in a cell type and activation state-dependent manner, yet their function has remained elusive. The Src family kinase members Lck and Lyn are key substrates for CD45 in T and B lymphocytes, respectively. CD45 lowers the threshold of antigen receptor signalling, which impacts T and B cell activation and development. CD45 also regulates antigen triggered Fc receptor signalling in mast cells and Toll-like receptor (TLR) signalling in dendritic cells, thus broadening the role of CD45 to other recognition receptors involved in adaptive and innate immunity. In addition, CD45 can affect immune cell adhesion and migration and can modulate cytokine production and signalling. Here we review what is known about the substrate specificity and regulation of CD45 and summarise its effect on immune cell signalling pathways, from its established role in T and B antigen receptor signalling to its emerging role regulating innate immune cell recognition and cytokine production.
AB - CD45 is a leukocyte specific transmembrane glycoprotein and a receptor-like protein tyrosine phosphatase (PTP). CD45 can be expressed as several alternatively spliced isoforms that differ in the extracellular domain. The isoforms are regulated in a cell type and activation state-dependent manner, yet their function has remained elusive. The Src family kinase members Lck and Lyn are key substrates for CD45 in T and B lymphocytes, respectively. CD45 lowers the threshold of antigen receptor signalling, which impacts T and B cell activation and development. CD45 also regulates antigen triggered Fc receptor signalling in mast cells and Toll-like receptor (TLR) signalling in dendritic cells, thus broadening the role of CD45 to other recognition receptors involved in adaptive and innate immunity. In addition, CD45 can affect immune cell adhesion and migration and can modulate cytokine production and signalling. Here we review what is known about the substrate specificity and regulation of CD45 and summarise its effect on immune cell signalling pathways, from its established role in T and B antigen receptor signalling to its emerging role regulating innate immune cell recognition and cytokine production.
KW - B-Lymphocytes/enzymology
KW - Leukocyte Common Antigens/metabolism
KW - Leukocytes/enzymology
KW - Protein Isoforms/metabolism
KW - Signal Transduction
KW - Substrate Specificity
KW - T-Lymphocytes/enzymology
KW - Toll-Like Receptors/metabolism
KW - src-Family Kinases/metabolism
U2 - 10.1016/j.cellsig.2009.10.003
DO - 10.1016/j.cellsig.2009.10.003
M3 - Review article
C2 - 19861160
VL - 22
SP - 339
EP - 348
JO - Cellular Signalling
JF - Cellular Signalling
SN - 0898-6568
IS - 3
ER -