PMID- 10446213
OWN - NLM
STAT- MEDLINE
DCOM- 19990909
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 34
DP  - 1999 Aug 20
TI  - Immune complex-induced integrin activation and L-plastin phosphorylation require 
      protein kinase A.
PG  - 24349-56
AB  - Integrins in resting leukocytes are poorly adhesive, and cell activation is
      required to induce integrin-mediated adhesion. We recently demonstrated a close
      correlation between phosphorylation of Ser(5) in L-plastin (LPL), a
      leukocyte-specific 67-kDa actin bundling protein, and activation of
      alpha(M)beta(2)-mediated adhesion in polymorphonuclear neutrophils (PMN) (Jones, 
      S. L., Wang, J., Turck, C. W., and Brown, E. J. (1998) Proc. Natl. Acad. Sci. U. 
      S. A. 95, 9331-9336). However, the kinase that phosphorylates LPL Ser(5) has not 
      been identified. We found that cAMP-dependent protein kinase (PKA), but not a
      variety of other serine kinases, can specifically phosphorylate LPL and
      LPL-derived peptides on Ser(5) in vitro. The cell-permeable cAMP analog
      8-bromo-cAMP and the adenylate cyclase activator forskolin both induce LPL
      phosphorylation in cells. Two PKA inhibitors, H89 and KT5720, inhibited immune
      complex (IC)-stimulated LPL phosphorylation as well as IC-induced activation of
      alpha(M)beta(2)-mediated adhesion in PMN. The dose response of H89 inhibition of 
      PMN adhesion correlated with its inhibition of LPL phosphorylation in response to
      IC. IC stimulation also transiently increased intracellular cAMP concentration in
      PMN. Thus, PKA functions in an integrin activation pathway initiated by IC
      binding to Fcgamma receptors in addition to its better known role as a negative
      regulator of cell activation by G protein-coupled receptors. In contrast, LPL
      Ser(5) phosphorylation and PMN adhesion induced by
      formylmethionyl-leucylphenylalanine or phorbol myristate acetate were not
      affected by PKA inhibitors, suggesting that a different kinase(s) is responsible 
      for LPL phosphorylation in response to these agonists. Phosphoinositidyl 3-kinase
      also is required for FcgammaR but not formylmethionyl-leucylphenylalanine- or
      phorbol myristate acetate-induced LPL phosphorylation and activation of
      alpha(M)beta(2). Two phosphoinositidyl 3-kinase inhibitors blocked
      FcgammaR-induced cAMP accumulation, demonstrating that this kinase acts upstream 
      of PKA. These data demonstrate a necessary role for PKA in IC-induced integrin
      activation and LPL phosphorylation.
FAU - Wang, J
AU  - Wang J
AD  - Division of Infectious Diseases and Program in Molecular Cell Biology, Washington
      University School of Medicine, St. Louis, Missouri 63110, USA.
FAU - Brown, E J
AU  - Brown EJ
LA  - eng
GR  - AI35811/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Antigen-Antibody Complex)
RN  - 0 (Carbazoles)
RN  - 0 (Indoles)
RN  - 0 (Isoquinolines)
RN  - 0 (Macrophage-1 Antigen)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Microfilament Proteins)
RN  - 0 (Phosphoproteins)
RN  - 0 (Pyrroles)
RN  - 0 (Receptors, IgG)
RN  - 0 (Sulfonamides)
RN  - 0 (plastin)
RN  - 452VLY9402 (Serine)
RN  - 58HV29I28S (KT 5720)
RN  - 59880-97-6 (N-Formylmethionine Leucyl-Phenylalanine)
RN  - E0399OZS9N (Cyclic AMP)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
RN  - M876330O56 (N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide)
RN  - NI40JAQ945 (Tetradecanoylphorbol Acetate)
SB  - IM
MH  - Amino Acid Sequence
MH  - Antigen-Antibody Complex/*physiology
MH  - *Carbazoles
MH  - Cell Adhesion
MH  - Cyclic AMP/biosynthesis
MH  - Cyclic AMP-Dependent Protein Kinases/*physiology
MH  - Indoles/pharmacology
MH  - Isoquinolines/pharmacology
MH  - Macrophage-1 Antigen/*metabolism
MH  - Membrane Glycoproteins
MH  - Microfilament Proteins
MH  - Molecular Sequence Data
MH  - N-Formylmethionine Leucyl-Phenylalanine/pharmacology
MH  - Neutrophils/physiology
MH  - Phosphatidylinositol 3-Kinases/physiology
MH  - Phosphoproteins/*metabolism
MH  - Phosphorylation
MH  - Pyrroles/pharmacology
MH  - Receptors, IgG/physiology
MH  - Serine/metabolism
MH  - *Sulfonamides
MH  - Tetradecanoylphorbol Acetate/pharmacology
EDAT- 1999/08/14 00:00
MHDA- 1999/08/14 00:01
CRDT- 1999/08/14 00:00
PHST- 1999/08/14 00:00 [pubmed]
PHST- 1999/08/14 00:01 [medline]
PHST- 1999/08/14 00:00 [entrez]
AID - 10.1074/jbc.274.34.24349 [doi]
AID - S0021-9258(19)55566-1 [pii]
PST - ppublish
SO  - J Biol Chem. 1999 Aug 20;274(34):24349-56. doi: 10.1074/jbc.274.34.24349.