Matrix valency regulates integrin-mediated lymphoid adhesion via Syk kinase.
Lymphocytes accumulate within the extracellular matrix (ECM) of tumor, wound, or inflammatory tissues. These tissues are largely comprised of polymerized adhesion proteins such as fibrin and fibronectin or their fragments. Nonactivated lymphoid cells attach preferentially to polymerized ECM proteins yet are unable to attach to monomeric forms or fragments of these proteins without previous activation. This adhesion event depends on the appropriate spacing of integrin adhesion sites. Adhesion of nonactivated lymphoid cells to polymeric ECM components results in activation of the antigen receptor-associated Syk kinase that accumulates in adhesion-promoting podosomes. In fact, activation of Syk by antigen or agonists, as well as expression of an activated Syk mutant in lymphoid cells, facilitates their adhesion to monomeric ECM proteins or their fragments. These results reveal a cooperative interaction between signals emanating from integrins and antigen receptors that can serve to regulate stable lymphoid cell adhesion and retention within a remodeling ECM.
Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA.
D G
DG
Stupack
E
E
Li
S A
SA
Silletti
J A
JA
Kehler
R L
RL
Geahlen
K
K
Hahn
G R
GR
Nemerow
D A
DA
Cheresh
D002448:Cell Adhesion / Q000502:physiology; D002460:Cell Line; D004792:Enzyme Precursors / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D016023:Integrins / Q000737:chemistry / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D008214:Lymphocytes / Q000166:cytology* / Q000378:metabolism*; D009369:Neoplasms / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D015398:Signal Transduction; D000072377:Syk Kinase; D014945:Wound Healing / Q000502:physiology
D004792:Enzyme Precursors; D016023:Integrins; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase