PMID- 9151903
OWN - NLM
STAT- MEDLINE
DCOM- 19970602
LR  - 20240213
IS  - 0022-1007 (Print)
IS  - 1540-9538 (Electronic)
IS  - 0022-1007 (Linking)
VI  - 185
IP  - 9
DP  - 1997 May 5
TI  - Lipopolysaccharide (LPS)-induced macrophage activation and signal transduction in 
      the absence of Src-family kinases Hck, Fgr, and Lyn.
PG  - 1661-70
AB  - Lipopolysaccharide (LPS) stimulates immune responses by interacting with the 
      membrane receptor CD14 to induce the generation of cytokines such as tumor 
      necrosis factor (TNF)-alpha, interleukin (IL)-1, and IL-6. The mechanism by which 
      the LPS signal is transduced from the extracellular environment to the nuclear 
      compartment is not well defined. Recently, an increasing amount of evidence 
      suggests that protein tyrosine kinases especially the Src-family kinases Hck, 
      Fgr, and Lyn, play important roles in LPS signaling. To directly address the 
      physiological function of Hck, Fgr and Lyn in LPS signaling, a genetic approach 
      has been used to generate null mutations of all three kinases in a single mouse 
      strain. hck-/-fgr-/-lyn-/- mice are moderately healthy and fertile; macrophages 
      cultured from these mice express normal levels of CD14 and no other Src-family 
      kinases were detected. Although the total protein phosphotyrosine level is 
      greatly reduced in macrophages derived from hck-/-fgr-/-lyn-/- mice, functional 
      analyses indicate that both elicited peritoneal (PEMs) and bone marrow-derived 
      macrophages (BMDMs) from triple mutant mice have no major defects in LPS-induced 
      activation. Nitrite production and cytokine secretion (IL-1, IL-6, and TNF-alpha) 
      are normal or even enhanced in hck-/-fgr-/-lyn-/- macrophages after LPS 
      stimulation. The development of tumor cell cytotoxicity is normal in triple 
      mutant BMDMs and only partially impaired in PEMs after LPS stimulation. 
      Furthermore, the activation of the ERK1/2 and JNK kinases, as well as the 
      transcription factor NF-kappaB, are the same in normal and mutant macrophages 
      after LPS stimulation. The current study provides direct evidence that three 
      Src-family kinases Hck, Fgr, and Lyn are not obligatory for LPS-initiated signal 
      transduction.
FAU - Meng, F
AU  - Meng F
AD  - Department of Laboratory Medicine, University of California, San Francisco 
      94143-0724, USA.
FAU - Lowell, C A
AU  - Lowell CA
LA  - eng
GR  - P50 HL054476/HL/NHLBI NIH HHS/United States
GR  - HL54476/HL/NHLBI NIH HHS/United States
GR  - T32 AI07334-09/AI/NIAID NIH HHS/United States
GR  - DK50267/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Exp Med
JT  - The Journal of experimental medicine
JID - 2985109R
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NF-kappa B)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 21820-51-9 (Phosphotyrosine)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.2 (Hck protein, mouse)
RN  - EC 2.7.10.2 (Proto-Oncogene Proteins c-hck)
RN  - EC 2.7.10.2 (lyn protein-tyrosine kinase)
RN  - EC 2.7.10.2 (proto-oncogene proteins c-fgr)
RN  - EC 2.7.10.2 (src-Family Kinases)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Animals
MH  - Calcium-Calmodulin-Dependent Protein Kinases/metabolism
MH  - Cytotoxicity, Immunologic
MH  - DNA-Binding Proteins/metabolism
MH  - Immunity, Cellular
MH  - JNK Mitogen-Activated Protein Kinases
MH  - Lipopolysaccharides/*immunology
MH  - *Macrophage Activation
MH  - Macrophages/enzymology/*physiology
MH  - Mice
MH  - Mice, Knockout
MH  - Mitogen-Activated Protein Kinase 1
MH  - Mitogen-Activated Protein Kinase 3
MH  - *Mitogen-Activated Protein Kinases
MH  - NF-kappa B/metabolism
MH  - Neoplasms, Experimental/immunology
MH  - Phosphorylation
MH  - Phosphotyrosine/metabolism
MH  - Protein-Tyrosine Kinases/*physiology
MH  - Proto-Oncogene Proteins/*physiology
MH  - Proto-Oncogene Proteins c-hck
MH  - Signal Transduction
MH  - Up-Regulation
MH  - src-Family Kinases/*physiology
PMC - PMC2196288
EDAT- 1997/05/05 00:00
MHDA- 1997/05/05 00:01
PMCR- 1997/11/05
CRDT- 1997/05/05 00:00
PHST- 1997/05/05 00:00 [pubmed]
PHST- 1997/05/05 00:01 [medline]
PHST- 1997/05/05 00:00 [entrez]
PHST- 1997/11/05 00:00 [pmc-release]
AID - 10.1084/jem.185.9.1661 [doi]
PST - ppublish
SO  - J Exp Med. 1997 May 5;185(9):1661-70. doi: 10.1084/jem.185.9.1661.