The engagement of beta1 integrins on promonocytic cells promotes phosphorylation of Syk and formation of a protein complex containing Lyn and beta1 integrin.
The protein-tyrosine kinase Syk participates in signal transduction pathways downstream from multiple immune recognition receptors. Recent evidence indicates that Syk is also functionally coupled to cell surface integrins, which mediate interactions between the actin cytoskeleton and extracellular matrix proteins. The interactions of undifferentiated, promonocytic HL60 or U937 cells with fibronectin or anti-beta1 integrin antibodies leads to an apparent activation and tyrosine phosphorylation of Syk that is independent of tight cellular adhesion and spreading. In response to fibronectin or anti-beta1 integrin antibodies, beta1 integrins become associated with a complex of proteins that include the Lyn protein tyrosine kinase and endogenous kinase substrates of 29 and 75-80 kDa. Lyn becomes transiently activated following integrin engagement and co-localizes with the actin cytoskeleton. These studies suggest a major role for Lyn in coupling beta1 integrins to the activation of Syk.
Miller
L A
LA
Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette 47907, USA.
Hong
J J
JJ
Kinch
M S
MS
Harrison
M L
ML
Geahlen
R L
RL
D000199:Actins / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation; D003599:Cytoskeleton / Q000378:metabolism; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000378:metabolism*; D018922:HL-60 Cells; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins; D009000:Monocytes / Q000166:cytology; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011817:Rabbits; D000072377:Syk Kinase; D020298:U937 Cells; D019061:src-Family Kinases / Q000378:metabolism*
D000199:Actins; D004792:Enzyme Precursors; D019012:Integrin beta1; D047908:Intracellular Signaling Peptides and Proteins; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases