PYK2 is an adhesion kinase in macrophages, localized in podosomes and activated by beta(2)-integrin ligation.
Pyk2 is a member of the focal adhesion kinase (FAK) family, highly expressed in the central nervous system and haemopoietic cells. Although Pyk2 is homologous to FAK, its role in signaling pathways was shown to be distinct from that of FAK. We show here that Pyk2 is highly expressed in peritoneal IC-21 macrophage and is tyrosine phosphorylated in response to cell attachment to fibronectin and fibrinogen. Upon IC-21 cell adhesion, Pyk2 tyrosine phosphorylation is inhibited by blocking antibodies to the integrin subunits alpha(M) and beta(2). Furthermore, Pyk2 is rapidly tyrosine phosphorylated in response to ligation of beta(2) integrins by antibodies. In migrating macrophages, Pyk2 localizes to perinuclear regions and to podosomes, where it is clustered with tyrosine phosphorylated proteins. Furthermore, in the podosomal ring structure, which surrounds the central actin core, Pyk2 co-localizes with vinculin, talin, and paxillin. In the podosomes, Pyk2 also co-localizes with the integrin alpha(M)beta(2). Lastly, reduction of Pyk2 expression in macrophages leads to inhibition of cell migration. We propose that Pyk2 is functionally linked to the formation of podosomes where it mediates the integrin-cytoskeleton interface and regulates cell spreading and migration.
Duong
L T
LT
Department of Bone Biology and Osteoporosis Research, Merck Research Laboratories, West Point, Pennsylvania 19486, USA. le_duong@merck.com
Rodan
G A
GA
D000818:Animals; D018821:CD18 Antigens / Q000378:metabolism*; D002448:Cell Adhesion; D002465:Cell Movement; D002478:Cells, Cultured; D004789:Enzyme Activation; D005434:Flow Cytometry; D051418:Focal Adhesion Kinase 2; D016023:Integrins / Q000378:metabolism; D016177:Macrophage-1 Antigen / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008856:Microscopy, Fluorescence; D010587:Phagocytosis; D010766:Phosphorylation; D010957:Plasmids / Q000378:metabolism; D011233:Precipitin Tests; D011505:Protein-Tyrosine Kinases / Q000378:metabolism* / Q000502:physiology*; D051381:Rats; D015398:Signal Transduction; D014162:Transfection
D018821:CD18 Antigens; D016023:Integrins; D016177:Macrophage-1 Antigen; D011505:Protein-Tyrosine Kinases; D051418:Focal Adhesion Kinase 2; C496053:Ptk2b protein, mouse; C496054:Ptk2b protein, rat