PMID- 10212274
OWN - NLM
STAT- MEDLINE
DCOM- 19990603
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 18
DP  - 1999 Apr 30
TI  - Characterization of the major physiologic phosphorylation site of human keratin
      19 and its role in filament organization.
PG  - 12861-6
AB  - Keratin polypeptide 19 (K19) is a type I intermediate filament protein that is
      expressed in stratified and simple-type epithelia. Little is known regarding K19 
      regulation or function, and the only other type I keratin that has been studied
      in terms of regulation is keratin 18 (K18). We characterized K19 phosphorylation 
      as a handle to study its function. In vivo, serine is the major phosphorylated
      residue, and phosphopeptide mapping of 32PO4-labeled K19 generates one major
      phosphopeptide. Edman degradation suggested that the radiolabeled phosphopeptide 
      represents K19 Ser-10 and/or Ser-35 phosphorylation. Mutation of Ser-10 or Ser-35
      followed by transfection confirmed that Ser-35 is the major K19 phosphorylation
      site. Transfection of Ser-35 --> Ala K19 showed a filament assembly defect as
      compared with normal or with Ser-10 --> Ala K19. Comparison of K18 and K19
      phosphorylation features in interphase cells showed that both are phosphorylated 
      primarily at a single site, preferentially in the soluble versus the insoluble
      keratin fractions. K19 has higher basal phosphorylation, whereas K18
      phosphorylation is far more sensitive to phosphatase type I and IIA inhibition.
      Our results demonstrate that Ser-35 is the major K19 interphase phosphorylation
      site and that it plays a role in keratin filament assembly. K19 and K18
      phosphorylations share some features but also have distinct properties that
      suggest different regulation of type I keratins within the same cells.
FAU - Zhou, X
AU  - Zhou X
AD  - Veterans Affairs Palo Alto Health Care System and Stanford University Digestive
      Disease Center, Palo Alto, California 94304, USA.
FAU - Liao, J
AU  - Liao J
FAU - Hu, L
AU  - Hu L
FAU - Feng, L
AU  - Feng L
FAU - Omary, M B
AU  - Omary MB
LA  - eng
GR  - DK07056/DK/NIDDK NIH HHS/United States
GR  - DK38707/DK/NIDDK NIH HHS/United States
GR  - DK47918/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
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  - 452VLY9402 (Serine)
RN  - 68238-35-7 (Keratins)
SB  - IM
MH  - Animals
MH  - Humans
MH  - Intermediate Filaments/*metabolism
MH  - Keratins/chemistry/genetics/*metabolism
MH  - Mutagenesis, Site-Directed
MH  - Phosphorylation
MH  - Serine/metabolism
EDAT- 1999/04/23 00:00
MHDA- 1999/04/23 00:01
CRDT- 1999/04/23 00:00
PHST- 1999/04/23 00:00 [pubmed]
PHST- 1999/04/23 00:01 [medline]
PHST- 1999/04/23 00:00 [entrez]
AID - 10.1074/jbc.274.18.12861 [doi]
AID - S0021-9258(19)73429-2 [pii]
PST - ppublish
SO  - J Biol Chem. 1999 Apr 30;274(18):12861-6. doi: 10.1074/jbc.274.18.12861.