ACTIVATION OF A NOVEL SERINE THREONINE KINASE THAT PHOSPHORYLATES C-FOS UPON STIMULATION OF T-LYMPHOCYTES AND B-LYMPHOCYTES VIA ANTIGEN ANDCYTOKINE RECEPTORS/
Ae. Nel et al., ACTIVATION OF A NOVEL SERINE THREONINE KINASE THAT PHOSPHORYLATES C-FOS UPON STIMULATION OF T-LYMPHOCYTES AND B-LYMPHOCYTES VIA ANTIGEN ANDCYTOKINE RECEPTORS/, The Journal of immunology, 152(9), 1994, pp. 4347-4357
Ligation of Ag receptors in T and B lymphocytes initiates signal trans
duction cascades which alter the expression of genes that regulate cel
lular proliferation and differentiation. The transmission of signals f
rom the membrane to the nucleus is mediated principally through the ac
tion of protein tyrosine and serine/threonine kinases. We have identif
ied and characterized a novel serine/threonine kinase that phosphoryla
ted the proto-oncogene product, c-Fos, and is termed Fos kinase. Fos k
inase was rapidly activated after ligation of the CD3 and CD2 receptor
s in Jurkat and normal human T lymphocytes and in response to IL-6 and
anti-IgM in the human B cell lines AF10 and Ramos, respectively. The
phorbol ester, PMA, was also a potent inducer of Fos kinase activity i
n all of the above populations, suggesting that PKC plays a role in th
e regulation of this enzyme. Fos kinase phosphorylates c-Fos at a site
near the C-terminus, as well as a peptide derived from this region (r
esidues 359-370, RKGSSSNEPSSD), and Fos peptide competitively inhibite
d c-Fos phosphorylation. Fos kinase was shown to be distinct from othe
r identified serine/threonine kinases, including protein kinase A, pro
tein kinase C, casein kinase II, MAP kinases, p70(S6K) and p90(RSK). F
OS kinase was purified by anion exchange chromatography and exhibited
an apparent M(r) 65,000 and isoelectric point = 6.1. Fos kinase may pl
ay a role in transcriptional regulation through its capacity to phosph
orylate c-Fos at a site required for expression of the transcriptional
transrepressive activity of this molecule. Moreover, its rapid activa
tion suggests it may have a wider role within signal transduction casc
ades in lymphocytes.