Highly stoichiometric, stable, and specific association of integrin alpha3beta1 with CD151 provides a major link to phosphatidylinositol 4-kinase, and may regulate cell migration.
Here we describe an association between alpha3beta1 integrin and transmembrane-4 superfamily (TM4SF) protein CD151. This association is maintained in relatively stringent detergents and thus is remarkably stable in comparison with previously reported integrin-TM4SF protein associations. Also, the association is highly specific (i.e., observed in vitro in absence of any other cell surface proteins), and highly stoichiometric (nearly 90% of alpha3beta1 associated with CD151). In addition, alpha3beta1 and CD151 appeared in parallel on many cell lines and showed nearly identical skin staining patterns. Compared with other integrins, alpha3beta1 exhibited a considerably higher level of associated phosphatidylinositol-4-kinase (PtdIns 4-kinase) activity, most of which was removed upon immunodepletion of CD151. Specificity for CD151 and PtdIns 4-kinase association resided in the extracellular domain of alpha3beta1, thus establishing a novel paradigm for the specific recruitment of an intracellular signaling molecule. Finally, antibodies to either CD151 or alpha3beta1 caused a approximately 88-92% reduction in neutrophil motility in response to f-Met-Leu-Phe on fibronectin, suggesting an functionally important role of these complexes in cell migration.
Yauch
R L
RL
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute and Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Berditchevski
F
F
Harler
M B
MB
Reichner
J
J
Hemler
M E
ME
D019870:1-Phosphatidylinositol 4-Kinase / Q000378:metabolism*; D015703:Antigens, CD / Q000235:genetics / Q000502:physiology*; D002634:Chemotaxis, Leukocyte; D005434:Flow Cytometry; D006706:Homeostasis; D006801:Humans; D039201:Integrin alpha3beta1; D016023:Integrins / Q000235:genetics / Q000502:physiology*; D020014:K562 Cells; D008562:Membrane Glycoproteins; D009504:Neutrophils / Q000502:physiology*; D015398:Signal Transduction; D060185:Tetraspanin 24; D060245:Tetraspanin 29; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; C554715:CD151 protein, human; C554869:CD9 protein, human; D039201:Integrin alpha3beta1; D016023:Integrins; D008562:Membrane Glycoproteins; D060185:Tetraspanin 24; D060245:Tetraspanin 29; D019870:1-Phosphatidylinositol 4-Kinase