Phospholipase Cgamma2 is essential in the functions of B cell and several Fc receptors.
Many receptors activate phospholipase Cgamma1 or -gamma2. To assess the role of PLCgamma2, we derived enzyme-deficient mice. The mice are viable but have decreased mature B cells, a block in pro-B cell differentiation, and B1 B cell deficiency. IgM receptor-induced Ca2+ flux and proliferation to B cell mitogens are absent. IgM, IgG2a, and IgG3 levels are reduced, and T cell-independent antibody production is absent. The similarity to Btk- or Blnk-deficient mice demonstrates that PLCgamma2 is downstream in Btk/Blnk signaling. FcRgamma signaling is also defective, resulting in a loss of collagen-induced platelet aggregation, mast cell FcepsilonR function, and NK cell FcgammaRIII and 2B4 function. The results define a signal transduction pathway broadly utilized by immunoglobulin superfamily receptors.
Department of Biochemistry, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
D
D
Wang
J
J
Feng
R
R
Wen
J C
JC
Marine
M Y
MY
Sangster
E
E
Parganas
A
A
Hoffmeyer
C W
CW
Jackson
J L
JL
Cleveland
P J
PJ
Murray
J N
JN
Ihle
D048868:Adaptor Proteins, Signal Transducing; D000077329:Agammaglobulinaemia Tyrosine Kinase; D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism / Q000502:physiology*; D001792:Blood Platelets / Q000502:physiology; D002352:Carrier Proteins / Q000378:metabolism; D006410:Hematopoiesis / Q000502:physiology; D007527:Isoenzymes / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051966:Phospholipase C gamma; D010750:Phosphoproteins / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism; D017452:Receptors, IgG / Q000378:metabolism / Q000502:physiology*; D010738:Type C Phospholipases / Q000235:genetics / Q000502:physiology*
D048868:Adaptor Proteins, Signal Transducing; C113939:B cell linker protein; D002352:Carrier Proteins; D007527:Isoenzymes; D010750:Phosphoproteins; D011947:Receptors, Antigen, B-Cell; D017452:Receptors, IgG; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; D010738:Type C Phospholipases; D051966:Phospholipase C gamma