ERK8, a new member of the mitogen-activated protein kinase family.
The ERKs are a subfamily of the MAPKs that have been implicated in cell growth and differentiation. By using the rat ERK7 cDNA to screen a human multiple tissue cDNA library, we identified a new member of the ERK family, ERK8, that shares 69% amino acid sequence identity with ERK7. Northern analysis demonstrates that ERK8 is present in a number of tissues with maximal expression in the lung and kidney. Fluorescence in situ hybridization localized the ERK8 gene to chromosome 8, band q24.3. Expression of ERK8 in COS cells and bacteria indicates that, in contrast to constitutively active ERK7, ERK8 has minimal basal kinase activity and a unique substrate profile. ERK8, which contains two SH3-binding motifs in its C-terminal region, associates with the c-Src SH3 domain in vitro and co-immunoprecipitates with c-Src in vivo. Co-transfection with either v-Src or a constitutively active c-Src increases ERK8 activation indicating that ERK8 can be activated downstream of c-Src. ERK8 is also activated following serum stimulation, and the extent of this activation is reduced by pretreatment with the specific Src family inhibitor PP2. The ERK8 activation by serum or Src was not affected by the MEK inhibitor U0126 indicating that activation of ERK8 does not require MEK1, MEK2, or MEK5. Although most closely related to ERK7, the relatively low sequence identity, minimal basal activity, and different substrate profile identify ERK8 as a distinct member of the MAPK family that is activated by an Src-dependent signaling pathway.
Abe
Mark K
MK
Department of Pediatrics, The Ben May Institute for Cancer Research, University of Chicago, Chicago, Illinois 60637, USA. markabe@ben-may.bsd.uchicago.edu
Saelzler
Matthew P
MP
Espinosa
Rafael
R
Kahle
Kristopher T
KT
Hershenson
Marc B
MB
Le Beau
Michelle M
MM
Rosner
Marsha Rich
MR
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D015153:Blotting, Western; D002070:Butadienes / Q000494:pharmacology; D019556:COS Cells; D002898:Chromosomes, Human, Pair 8; D018076:DNA, Complementary / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005091:Exons; D048049:Extracellular Signal-Regulated MAP Kinases; D015723:Gene Library; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007438:Introns; D020935:MAP Kinase Signaling System; D020928:Mitogen-Activated Protein Kinases / Q000096:biosynthesis* / Q000737:chemistry* / Q000378:metabolism*; D008969:Molecular Sequence Data; D009570:Nitriles / Q000494:pharmacology; D010802:Phylogeny; D010957:Plasmids / Q000378:metabolism; D011233:Precipitin Tests; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D014018:Tissue Distribution; D014162:Transfection; D019061:src-Family Kinases / Q000378:metabolism
D002070:Butadienes; D018076:DNA, Complementary; D004791:Enzyme Inhibitors; D009570:Nitriles; D011993:Recombinant Fusion Proteins; C113580:U 0126; D005982:Glutathione Transferase; D019061:src-Family Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; C456320:MAPK15 protein, human; D020928:Mitogen-Activated Protein Kinases