Hematopoietic cell kinase (Hck) isoforms and phagocyte duties - from signaling and actin reorganization to migration and phagocytosis.
The activity of hematopoietic cell kinase (Hck), a member of the Src family kinases, is modulated by regulatory mechanisms leading to distinct protein conformations with gradual levels of activity. Hck is mostly expressed in phagocytes as two isoforms, p59Hck and p61Hck, which show distinct subcellular localizations and trigger distinct phenotypes when expressed ectopically in fibroblasts. Hck has been reported to be involved in phagocytosis, adhesion and migration, and to regulate formation of membrane protrusions, lysosome exocytosis, podosome formation, and actin polymerization. The present review focuses on the mechanisms regulating Hck activity as well as on the functions of Hck isoforms in phagocytes, and presents selected examples of Hck substrates and/or adaptors shown to interact with the kinase in myeloid cells. Deciphering Hck signaling pathways is a challenge to progress in the understanding of innate immune responses and pathologies involving phagocytes such as inflammatory diseases, leukemia, and human immunodeficiency virus-1 (HIV-1) infection.
Département Mécanismes Moléculaires des Infections Mycobactériennes, Institut de Pharmacologie et de Biologie Structurale, Centre National de la Recherche Scientifique UMR 5089, F-31077 Toulouse cedex, France.
Romain
R
Guiet
Renaud
R
Poincloux
Jerôme
J
Castandet
Louis
L
Marois
Arnaud
A
Labrousse
Véronique
V
Le Cabec
Isabelle
I
Maridonneau-Parini
D000199:Actins / Q000378:metabolism*; D000818:Animals; D002465:Cell Movement / Q000502:physiology*; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism; D051379:Mice; D010586:Phagocytes / Q000166:cytology / Q000201:enzymology*; D010587:Phagocytosis / Q000502:physiology*; D020033:Protein Isoforms / Q000378:metabolism; D051572:Proto-Oncogene Proteins c-hck / Q000378:metabolism*; D015398:Signal Transduction; D019061:src-Family Kinases / Q000378:metabolism
D000199:Actins; D020033:Protein Isoforms; D051572:Proto-Oncogene Proteins c-hck; D019061:src-Family Kinases