Temporal activation of nontransmembrane protein-tyrosine kinases following mast cell Fc epsilon RI engagement.
One of the primary responses observed following antigen-induced cross-linking in mast cells is an increase in the phosphorylation of certain cellular proteins on tyrosine residues. Stimulation of protein-tyrosine kinase activity appears to be necessary for induction of downstream responses such as degranulation. The role of nonreceptor protein-tyrosine kinases in the signal transduction pathway initiated by Fc epsilon RI engagement in an interleukin-3-dependent mast cell line has been examined. The results presented here show that the enzymatic activity of Lyn is increased within seconds of receptor engagement. Syk activity also undergoes a rapid and transient increase, reaching a peak at approximately 30 s. Similarly, the activity of Fer, representing a third class of nontransmembrane protein-tyrosine kinase increases as well, with its activity peak reached at 1 min poststimulation. The enzymatic activities of Syk and Fer were found to correspond to anti-phosphotyrosine antibody reactivity. Phosphorylation of tyrosine residues of the beta and gamma chains of Fc epsilon RI increased concomitant with increased protein-tyrosine kinase activity. These results indicate that at least three classes of nontransmembrane protein-tyrosine kinases are involved in mast cell FceRI signaling and that the activation of these classes of enzymes is temporally regulated.
Penhallow
R C
RC
Department of Molecular Biology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543, USA.
Class
K
K
Sonoda
H
H
Bolen
J B
JB
Rowley
R B
RB
D000818:Animals; D015550:Cell Degranulation; D002460:Cell Line; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D007700:Kinetics; D008407:Mast Cells / Q000201:enzymology* / Q000276:immunology* / Q000502:physiology; D051379:Mice; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000145:classification / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D017455:Receptors, IgE / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction; D000072377:Syk Kinase; D019061:src-Family Kinases / Q000378:metabolism
D004792:Enzyme Precursors; D047908:Intracellular Signaling Peptides and Proteins; D011518:Proto-Oncogene Proteins; D017455:Receptors, IgE; C052602:proto-oncogene protein c-fes-fps; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; C000606897:Syk protein, mouse; D019061:src-Family Kinases