Identification of Rlk, a novel protein tyrosine kinase with predominant expression in the T cell lineage.
The control of phosphorylation by protein tyrosine kinases represents an important regulatory mechanism in T cell growth, function, and differentiation. We have identified a 62-kDa murine protein tyrosine kinase predominantly expressed within the T cell lineage, which we have termed Rlk (for Resting lymphocyte kinase). rlk mRNA was found to be expressed in the fetal thymus as early as day 13 of embryonic development as well as in adult thymus and mature resting peripheral T cells. The sequence of rlk showed that it is most closely related to the subfamily of cytoplasmic tyrosine kinases that includes the Btk, Itk, and Tec proteins. However, Rlk differs from these kinases by virtue of its unique aminoterminal domain, which lacks a region of pleckstrin homology common to the other members of this protein subfamily. Examination of rlk abundance within different T cell subpopulations revealed preferential expression in Th1 relative to Th2 T cell clones, suggesting a possible role in signal transduction pathways that selectively regulate cytokine production in mature CD4+ T cell subsets. Rlk thus represents a novel cytoplasmic tyrosine kinase with potential functions in intrathymic T cell development and mature T cell signaling.
Hu
Q
Q
Immunobiology Program, Alexion Pharmaceuticals, Inc., New Haven, Connecticut 06511.
Davidson
D
D
Schwartzberg
P L
PL
Macchiarini
F
F
Lenardo
M J
MJ
Bluestone
J A
JA
Matis
L A
LA
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D003001:Cloning, Molecular; D017124:Conserved Sequence; D017931:DNA Primers; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009928:Organ Specificity; D010455:Peptides / Q000138:chemical synthesis / Q000494:pharmacology; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism; D015183:Restriction Mapping; D017386:Sequence Homology, Amino Acid; D013601:T-Lymphocytes / Q000201:enzymology*; D014407:Tumor Cells, Cultured
D017931:DNA Primers; D010455:Peptides; D011994:Recombinant Proteins; C089848:Tec protein-tyrosine kinase; D011505:Protein-Tyrosine Kinases