BIOMAT Database Logo BIOMAT Database Logo

Impaired CD28-mediated interleukin 2 production and proliferation in stress kinase SAPK/ERK1 kinase (SEK1)/mitogen-activated protein kinase kinase 4 (MKK4)-deficient T lymphocytes. 1997

H Nishina, and M Bachmann, and A J Oliveira-dos-Santos, and I Kozieradzki, and K D Fischer, and B Odermatt, and A Wakeham, and A Shahinian, and H Takimoto, and A Bernstein, and T W Mak, and J R Woodgett, and P S Ohashi, and J M Penninger
Amgen Institute and Ontario Cancer Institute, Department of Medical Biophysics and Immunology, University of Toronto, M5G 2C1 Toronto, Ontario, Canada.

The dual specific kinase SAPK/ERK1 kinase (SEK1; mitogen-activated protein kinase kinase 4/Jun NH2 terminal kinase [ JNK] kinase) is a direct activator of stress-activated protein kinases ([SAPKs]/JNKs) in response to CD28 costimulation, CD40 signaling, or activation of the germinal center kinase. Here we show that SEK1(-/-) recombination-activating gene (RAG)2(-/-) chimeric mice have a partial block in B cell maturation. However, peripheral B cells displayed normal responses to IL-4, IgM, and CD40 cross-linking. SEK1(-/-) peripheral T cells showed decreased proliferation and IL-2 production after CD28 costimulation and PMA/Ca2+ ionophore activation. Although CD28 expression was absolutely crucial to generate vesicular stomatitis virus (VSV)-specific germinal centers, SEK1(-/-)RAG2(-/-) chimeras mounted a protective antiviral B cell response, exhibited normal IgG class switching, and made germinal centers in response to VSV. Interestingly, PMA/Ca2+ ionophore stimulation, which mimics TCR-CD3 and CD28-mediated signal transduction, induced SAPK/JNK activation in peripheral T cells, but not in thymocytes, from SEK1(-/-) mice. These results show that signaling pathways for SAPK activation are developmentally regulated in T cells. Although SEK1(-/-) thymocytes failed to induce SAPK/JNK in response to PMA/Ca2+ ionophore, SEK1(-/-)RAG2(-/-) thymocytes proliferated and made IL-2 after PMA/Ca2+ ionophore and CD3/CD28 stimulation, albeit at significantly lower levels compared to SEK1(+/+)RAG2(-/-) thymocytes, implying that CD28 costimulation and PMA/Ca2+ ionophore-triggered signaling pathways exist that can mediate proliferation and IL-2 production independently of SAPK activation. Our data provide the first genetic evidence that SEK1 is an important effector molecule that relays CD28 signaling to IL-2 production and T cell proliferation.

UI MeSH Term Description Entries
D007134 Immunoglobulin Switch Region A site located in the INTRONS at the 5' end of each constant region segment of a immunoglobulin heavy-chain gene where recombination (or rearrangement) occur during IMMUNOGLOBULIN CLASS SWITCHING. Ig switch regions are found on genes encoding all five classes (IMMUNOGLOBULIN ISOTYPES) of IMMUNOGLOBULIN HEAVY CHAINS. Ig Switch Region,Switch Region, Immunoglobulin,Heavy-Chain Mu Switch Region,Ig Switch Sequences,Ig Switch Regions,Ig Switch Sequence,Immunoglobulin Switch Regions,Region, Ig Switch,Region, Immunoglobulin Switch,Regions, Ig Switch,Regions, Immunoglobulin Switch,Sequence, Ig Switch,Sequences, Ig Switch,Switch Region, Ig,Switch Regions, Ig,Switch Regions, Immunoglobulin,Switch Sequence, Ig,Switch Sequences, Ig
D007376 Interleukin-2 A soluble substance elaborated by antigen- or mitogen-stimulated T-LYMPHOCYTES which induces DNA synthesis in naive lymphocytes. IL-2,Lymphocyte Mitogenic Factor,T-Cell Growth Factor,TCGF,IL2,Interleukin II,Interleukine 2,RU 49637,RU-49637,Ro-23-6019,Ro-236019,T-Cell Stimulating Factor,Thymocyte Stimulating Factor,Interleukin 2,Mitogenic Factor, Lymphocyte,RU49637,Ro 23 6019,Ro 236019,Ro236019,T Cell Growth Factor,T Cell Stimulating Factor
D008213 Lymphocyte Activation Morphologic alteration of small B LYMPHOCYTES or T LYMPHOCYTES in culture into large blast-like cells able to synthesize DNA and RNA and to divide mitotically. It is induced by INTERLEUKINS; MITOGENS such as PHYTOHEMAGGLUTININS, and by specific ANTIGENS. It may also occur in vivo as in GRAFT REJECTION. Blast Transformation,Blastogenesis,Lymphoblast Transformation,Lymphocyte Stimulation,Lymphocyte Transformation,Transformation, Blast,Transformation, Lymphoblast,Transformation, Lymphocyte,Activation, Lymphocyte,Stimulation, Lymphocyte
D011494 Protein Kinases A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein. Protein Kinase,Kinase, Protein,Kinases, Protein
D011505 Protein-Tyrosine Kinases Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors. Tyrosine Protein Kinase,Tyrosine-Specific Protein Kinase,Protein-Tyrosine Kinase,Tyrosine Kinase,Tyrosine Protein Kinases,Tyrosine-Specific Protein Kinases,Tyrosylprotein Kinase,Kinase, Protein-Tyrosine,Kinase, Tyrosine,Kinase, Tyrosine Protein,Kinase, Tyrosine-Specific Protein,Kinase, Tyrosylprotein,Kinases, Protein-Tyrosine,Kinases, Tyrosine Protein,Kinases, Tyrosine-Specific Protein,Protein Kinase, Tyrosine-Specific,Protein Kinases, Tyrosine,Protein Kinases, Tyrosine-Specific,Protein Tyrosine Kinase,Protein Tyrosine Kinases,Tyrosine Specific Protein Kinase,Tyrosine Specific Protein Kinases
D011995 Recombination, Genetic Production of new arrangements of DNA by various mechanisms such as assortment and segregation, CROSSING OVER; GENE CONVERSION; GENETIC TRANSFORMATION; GENETIC CONJUGATION; GENETIC TRANSDUCTION; or mixed infection of viruses. Genetic Recombination,Recombination,Genetic Recombinations,Recombinations,Recombinations, Genetic
D002454 Cell Differentiation Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs. Differentiation, Cell,Cell Differentiations,Differentiations, Cell
D002678 Chimera An individual that contains cell populations derived from different zygotes. Hybrids,Chimeras,Hybrid
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001402 B-Lymphocytes Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation. B-Cells, Lymphocyte,B-Lymphocyte,Bursa-Dependent Lymphocytes,B Cells, Lymphocyte,B Lymphocyte,B Lymphocytes,B-Cell, Lymphocyte,Bursa Dependent Lymphocytes,Bursa-Dependent Lymphocyte,Lymphocyte B-Cell,Lymphocyte B-Cells,Lymphocyte, Bursa-Dependent,Lymphocytes, Bursa-Dependent

Related Publications

H Nishina, and M Bachmann, and A J Oliveira-dos-Santos, and I Kozieradzki, and K D Fischer, and B Odermatt, and A Wakeham, and A Shahinian, and H Takimoto, and A Bernstein, and T W Mak, and J R Woodgett, and P S Ohashi, and J M Penninger
Mitogen-activated protein kinase kinase 4 (MKK4).
June 2000, The international journal of biochemistry & cell biology,
H Nishina, and M Bachmann, and A J Oliveira-dos-Santos, and I Kozieradzki, and K D Fischer, and B Odermatt, and A Wakeham, and A Shahinian, and H Takimoto, and A Bernstein, and T W Mak, and J R Woodgett, and P S Ohashi, and J M Penninger
Induction of cyclooxygenase-2 by the activated MEKK1 --> SEK1/MKK4 --> p38 mitogen-activated protein kinase pathway.
May 1998, The Journal of biological chemistry,
H Nishina, and M Bachmann, and A J Oliveira-dos-Santos, and I Kozieradzki, and K D Fischer, and B Odermatt, and A Wakeham, and A Shahinian, and H Takimoto, and A Bernstein, and T W Mak, and J R Woodgett, and P S Ohashi, and J M Penninger
Mitogen-activated protein kinase kinase 4/stress-activated protein/Erk kinase 1 (MKK4/SEK1), a prostate cancer metastasis suppressor gene encoded by human chromosome 17.
November 1999, Cancer research,
H Nishina, and M Bachmann, and A J Oliveira-dos-Santos, and I Kozieradzki, and K D Fischer, and B Odermatt, and A Wakeham, and A Shahinian, and H Takimoto, and A Bernstein, and T W Mak, and J R Woodgett, and P S Ohashi, and J M Penninger
Impaired TCR-mediated apoptosis and Bcl-XL expression in T cells lacking the stress kinase activator SEK1/MKK4.
October 1998, Journal of immunology (Baltimore, Md. : 1950),
H Nishina, and M Bachmann, and A J Oliveira-dos-Santos, and I Kozieradzki, and K D Fischer, and B Odermatt, and A Wakeham, and A Shahinian, and H Takimoto, and A Bernstein, and T W Mak, and J R Woodgett, and P S Ohashi, and J M Penninger
Impaired synergistic activation of stress-activated protein kinase SAPK/JNK in mouse embryonic stem cells lacking SEK1/MKK4: different contribution of SEK2/MKK7 isoforms to the synergistic activation.
August 2001, The Journal of biological chemistry,
H Nishina, and M Bachmann, and A J Oliveira-dos-Santos, and I Kozieradzki, and K D Fischer, and B Odermatt, and A Wakeham, and A Shahinian, and H Takimoto, and A Bernstein, and T W Mak, and J R Woodgett, and P S Ohashi, and J M Penninger
Potential role of phospholipase D2 in increasing interleukin-2 production by T-lymphocytes through activation of mitogen-activated protein kinases ERK1/ERK2.
May 2008, Biochimica et biophysica acta,
H Nishina, and M Bachmann, and A J Oliveira-dos-Santos, and I Kozieradzki, and K D Fischer, and B Odermatt, and A Wakeham, and A Shahinian, and H Takimoto, and A Bernstein, and T W Mak, and J R Woodgett, and P S Ohashi, and J M Penninger
Synergistic activation of stress-activated protein kinase 1/c-Jun N-terminal kinase (SAPK1/JNK) isoforms by mitogen-activated protein kinase kinase 4 (MKK4) and MKK7.
November 2000, The Biochemical journal,
H Nishina, and M Bachmann, and A J Oliveira-dos-Santos, and I Kozieradzki, and K D Fischer, and B Odermatt, and A Wakeham, and A Shahinian, and H Takimoto, and A Bernstein, and T W Mak, and J R Woodgett, and P S Ohashi, and J M Penninger
Scaffold modified Vemurafenib analogues as highly selective mitogen activated protein kinase kinase 4 (MKK4) inhibitors.
October 2022, European journal of medicinal chemistry,
H Nishina, and M Bachmann, and A J Oliveira-dos-Santos, and I Kozieradzki, and K D Fischer, and B Odermatt, and A Wakeham, and A Shahinian, and H Takimoto, and A Bernstein, and T W Mak, and J R Woodgett, and P S Ohashi, and J M Penninger
Mitogen-activated protein kinase signalling and ERK1/2 bistability in asthma.
February 2011, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology,
H Nishina, and M Bachmann, and A J Oliveira-dos-Santos, and I Kozieradzki, and K D Fischer, and B Odermatt, and A Wakeham, and A Shahinian, and H Takimoto, and A Bernstein, and T W Mak, and J R Woodgett, and P S Ohashi, and J M Penninger
Apolipoprotein E inhibition of proliferation of mitogen-activated T lymphocytes: production of interleukin 2 with reduced biological activity.
December 1994, Cellular immunology,
Copied contents to your clipboard!