PMID- 10373551
OWN - NLM
STAT- MEDLINE
DCOM- 19990722
LR  - 20210526
IS  - 0270-7306 (Print)
IS  - 0270-7306 (Linking)
VI  - 19
IP  - 7
DP  - 1999 Jul
TI  - Regulation of nuclear localization and transcriptional activity of TFII-I by
      Bruton's tyrosine kinase.
PG  - 5014-24
AB  - Bruton's tyrosine kinase (Btk) is required for normal B-cell development, as
      defects in Btk lead to X-linked immunodeficiency (xid) in mice and X-linked
      agammaglobulinemia (XLA) in humans. Here we demonstrate a functional interaction 
      between the multifunctional transcription factor TFII-I and Btk. Ectopic
      expression of wild-type Btk enhances TFII-I-mediated transcriptional activation
      and its tyrosine phosphorylation in transient-transfection assays. Mutation of
      Btk in either the PH domain (R28C, as in the murine xid mutation) or the kinase
      domain (K430E) compromises its ability to enhance both the tyrosine
      phosphorylation and the transcriptional activity of TFII-I. TFII-I associates
      constitutively in vivo with wild-type Btk and kinase-inactive Btk but not xid
      Btk. However, membrane immunoglobulin M cross-linking in B cells leads to
      dissociation of TFII-I from Btk. We further show that while TFII-I is found in
      both the nucleus and cytoplasm of wild-type and xid primary resting B cells,
      nuclear TFII-I is greater in xid B cells. Most strikingly, receptor cross-linking
      of wild-type (but not xid) B cells results in increased nuclear import of TFII-I.
      Taken together, these data suggest that although the PH domain of Btk is
      primarily responsible for its physical interaction with TFII-I, an intact kinase 
      domain of Btk is required to enhance transcriptional activity of TFII-I in the
      nucleus. Thus, mutations impairing the physical and/or functional association
      between TFII-I and Btk may result in diminished TFII-I-dependent transcription
      and contribute to defective B-cell development and/or function.
FAU - Novina, C D
AU  - Novina CD
AD  - Department of Pathology and Program in Immunology, Tufts University School of
      Medicine, Boston, Massachusetts 02111, USA.
FAU - Kumar, S
AU  - Kumar S
FAU - Bajpai, U
AU  - Bajpai U
FAU - Cheriyath, V
AU  - Cheriyath V
FAU - Zhang, K
AU  - Zhang K
FAU - Pillai, S
AU  - Pillai S
FAU - Wortis, H H
AU  - Wortis HH
FAU - Roy, A L
AU  - Roy AL
LA  - eng
GR  - R01 AI033507/AI/NIAID NIH HHS/United States
GR  - AI 15803/AI/NIAID NIH HHS/United States
GR  - AI 33507/AI/NIAID NIH HHS/United States
GR  - CA 69618/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Mol Cell Biol
JT  - Molecular and cellular biology
JID - 8109087
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Transcription Factors)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.2 (Agammaglobulinaemia Tyrosine Kinase)
RN  - EC 2.7.10.2 (BTK protein, human)
RN  - EC 2.7.10.2 (Btk protein, mouse)
SB  - IM
MH  - Agammaglobulinaemia Tyrosine Kinase
MH  - Animals
MH  - B-Lymphocytes/enzymology/physiology
MH  - COS Cells
MH  - Cell Line
MH  - Cell Nucleus/metabolism
MH  - DNA-Binding Proteins/genetics/*metabolism
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mutagenesis
MH  - Protein-Tyrosine Kinases/genetics/*metabolism
MH  - Subcellular Fractions
MH  - Transcription Factors/genetics/*metabolism
MH  - Transcription, Genetic
MH  - *Transcriptional Activation
PMC - PMC84330
EDAT- 1999/06/22 00:00
MHDA- 1999/06/22 00:01
CRDT- 1999/06/22 00:00
PHST- 1999/06/22 00:00 [pubmed]
PHST- 1999/06/22 00:01 [medline]
PHST- 1999/06/22 00:00 [entrez]
AID - 10.1128/MCB.19.7.5014 [doi]
PST - ppublish
SO  - Mol Cell Biol. 1999 Jul;19(7):5014-24. doi: 10.1128/MCB.19.7.5014.