ERKs: a family of protein-serine/threonine kinases that are activated and tyrosine phosphorylated in response to insulin and NGF.
We recently described the purification and cloning of extracellular signal-regulated kinase 1 (ERK1), which appears to play a pivotal role in converting tyrosine phosphorylation into the serine/threonine phosphorylations that regulate downstream events. We now describe cloning and characterization of two ERK1-related kinases, ERK2 and ERK3, and provide evidence suggesting that there are additional ERK family members. At least two of the ERKs are activated in response to growth factors; their activations correlate with tyrosine phophorylation, but also depend on additional modifications. Transcripts corresponding to the three cloned ERKs are distinctly regulated both in vivo and in a differentiating cell line. Thus, this family of kinases may serve as intermediates that depend on tyrosine phosphorylation to activate serine/threonine phosphorylation cascades. Individual family members may mediate responses in different developmental stages, in different cell types, or following exposure to different extracellular signals.
Boulton
Teri G
TG
Department of Pharmacology, University of Texas Southwestern Graduate School of Biomedical Sciences, Dallas 75235-9041.
Nye
Steven H
SH
Robbins
David J
DJ
Ip
Nancy Y
NY
Radziejewska
Elizabeth
E
Morgenbesser
Sharon D
SD
DePinho
Ronald A
RA
Panayotatos
Nikos
N
Cobb
Melanie H
MH
Yancopoulos
George D
GD
D000595:Amino Acid Sequence; D000818:Animals; D001253:Astrocytes / Q000201:enzymology; D001483:Base Sequence; D002460:Cell Line; D002478:Cells, Cultured; D003001:Cloning, Molecular; D004789:Enzyme Activation; D006624:Hippocampus / Q000201:enzymology; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048053:Mitogen-Activated Protein Kinase 6; D020928:Mitogen-Activated Protein Kinases; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009928:Organ Specificity; D010766:Phosphorylation; D011494:Protein Kinases / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D011544:Pseudogenes; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D012689:Sequence Homology, Nucleic Acid; D013724:Teratoma; D014443:Tyrosine
D007328:Insulin; D009414:Nerve Growth Factors; D011994:Recombinant Proteins; D014443:Tyrosine; D011494:Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048053:Mitogen-Activated Protein Kinase 6; D020928:Mitogen-Activated Protein Kinases