fyn tyrosine kinase is involved in keratinocyte differentiation control.
Induction of tyrosine phosphorylation is an early and specific event which is required for mouse keratinocyte differentiation to occur, in response to both calcium and TPA (12-0-tetradecanoylphorbol-13-acetate). We report here that there is an increase of tyrosine kinase activity immunoprecipitable with anti-phosphotyrosine antibodies specifically in response to calcium--and a number of other divalent cations--within 2 min of exposure. Such an activity does not correspond to any of the known tyrosine kinases that were tested. A second tyrosine kinase activity is induced in response to both calcium and TPA, and has been identified as fyn, a nonreceptor tyrosine kinase of the src family. fyn activation is induced in keratinocytes within 6 hr of calcium exposure, but already within 2 min of TPA treatment. Cortactin, a p80-85 substrate of src- and fyn-related kinases that localizes with actin at cell adhesion sites, is increasingly tyrosine phosphorylated in calcium- and TPA-induced differentiation, with a time course which parallels that of fyn activation. Keratinocytes with a specific disruption of the fyn, but not yes kinase gene show no induction of phosphorylation of p80-85 proteins, and are significantly altered in their differentiation response both in vitro and in vivo. Thus, at least two tyrosine kinase activities are induced in keratinocyte differentiation, one of which has been identified as fyn and shown to be specifically involved in this process.
Calautti
E
E
Cutaneous Biology Research Center, Massachusetts General Hospital, Charlestown 02129, USA.
Missero
C
C
Stein
P L
PL
Ezzell
R M
RM
Dotto
G P
GP
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D051356:Cortactin; D003599:Cytoskeleton / Q000648:ultrastructure; D004790:Enzyme Induction; D015603:Keratinocytes / Q000187:drug effects / Q000201:enzymology / Q000502:physiology* / Q000648:ultrastructure; D051379:Mice; D018632:Mice, Inbred SENCAR; D008817:Mice, Mutant Strains; D008840:Microfilament Proteins / Q000378:metabolism; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000276:immunology; D011233:Precipitin Tests; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D051076:Proto-Oncogene Proteins c-fyn; D051575:Proto-Oncogene Proteins c-yes; D012867:Skin / Q000166:cytology / Q000196:embryology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors; D011503:Transglutaminases / Q000096:biosynthesis; D019061:src-Family Kinases
D051356:Cortactin; C495869:Cttn protein, mouse; D008840:Microfilament Proteins; D011518:Proto-Oncogene Proteins; D019000:Phosphotyrosine; D011503:Transglutaminases; D011505:Protein-Tyrosine Kinases; C494960:Fyn protein, mouse; D051076:Proto-Oncogene Proteins c-fyn; D051575:Proto-Oncogene Proteins c-yes; C496639:Yes1 protein, mouse; D019061:src-Family Kinases; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium