Early signal protein expression profiles in basophils: a population study.
IgE-mediated histamine release from peripheral blood basophils is highly variable within the general population. Recent studies have shown that the ability of anti-IgE antibody to induce release can be predicted reasonably well by knowing the level of syk expression in the cells. The current study expands a previous survey to include 14 additional early elements known to be involved in activation and deactivation of basophils and showed that with the exception of syk, the variance of expression of 19 other elements (lyn, fyn, csk, cbp/PAG, CIN85, Bob1, c-cbl, SHIP1, SHIP2, p85alpha, p110delta, btk, PLCgamma1, PLCgamma2, SHP-1, PTEN, SOS2, CRACM1, and IL-3Ralpha) was narrow despite a broad range of functional capability in the basophils under study. With syk as the only element with high variance and well-correlated to maximum histamine release and cellular sensitivity, this survey examined the expression levels of two proteins thought to regulate syk expression: Bob1/OCA-B and CIN85. Expression of CIN85 was not correlated to syk expression, but Bob1 expression was negatively correlated to expression of syk and maximum histamine release. However, the expected behavior for this protein should have been as a protector of post-translational syk loss and therefore, positively correlated. Previous studies suggested that post-translational control mechanisms regulated syk expression. However, in this study, steady-state mRNA levels for syk in resting basophils showed a correlation with syk protein expression levels (r=0.593). It is concluded that with the exception of syk expression, the expression of 19 early signaling elements is tightly regulated and that a component of the regulation of syk may be related to control of transcription or processing of syk mRNA.
Johns Hopkins Asthma and Allergy Center, Baltimore, MD 21224, USA.
Susan
S
Ishmael
Donald
D
MacGlashan
D000328:Adult; D001491:Basophils / Q000378:metabolism*; D015331:Cohort Studies; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation / Q000276:immunology*; D006632:Histamine / Q000378:metabolism*; D006801:Humans; D007073:Immunoglobulin E / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011499:Protein Processing, Post-Translational / Q000235:genetics / Q000276:immunology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D050436:Regulatory Elements, Transcriptional / Q000276:immunology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D000072377:Syk Kinase; D013997:Time Factors; D015534:Trans-Activators / Q000378:metabolism; D055815:Young Adult
D047908:Intracellular Signaling Peptides and Proteins; C091546:POU2AF1 protein, human; D012333:RNA, Messenger; D015534:Trans-Activators; D007073:Immunoglobulin E; D006632:Histamine; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase