Identification of an early-growth-response gene encoding a novel putative protein kinase.
Early-growth-response genes, also known as immediate-early genes, play important roles in regulating cell proliferation. We have identified a new type of early-growth-response gene product, a 77,811-Da putative serine/threonine kinase, which is highly inducible by serum and phorbol ester. mRNA encoding this putative kinase is markedly elevated within 1 h after treatment with mitogen, and this induction is synergistically increased by cycloheximide. Dexamethasone blocks serum induction of the kinase mRNA, as does transformation by v-Ki-ras. The kinase mRNA was detected in mouse brain, lung, and heart. This new putative kinase, which we term Snk, for serum-inducible kinase, showed similarity in its proposed catalytic domain to many other protein kinases; however, no other kinase showed enough sequence similarity with Snk to suggest the existence of a common function. Hence, Snk represents a new type of protein kinase involved in the early mitogenic response whose activity is transcriptionally and posttranscriptionally regulated.
Simmons
D L
DL
Department of Chemistry, Brigham Young University, Provo, Utah 84602.
Neel
B G
BG
Stevens
R
R
Evett
G
G
Erikson
R L
RL
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D004247:DNA; D005786:Gene Expression Regulation; D005938:Glucocorticoids / Q000502:physiology; D008297:Male; D051379:Mice; D008934:Mitogens / Q000494:pharmacology; D008969:Molecular Sequence Data; D009928:Organ Specificity / Q000235:genetics; D011494:Protein Kinases / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012689:Sequence Homology, Nucleic Acid; D014158:Transcription, Genetic
D005938:Glucocorticoids; D008934:Mitogens; D012333:RNA, Messenger; D004247:DNA; D011494:Protein Kinases