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CD44-initiated Cell Spreading Induces Pyk2 Phosphorylation, Is Mediated by Src Family Kinases, and Is Negatively Regulated by CD45

CD44-initiated Cell Spreading Induces Pyk2 Phosphorylation, Is Mediated by Src Family Kinases, and Is Negatively Regulated by CD45

R Li, N Wong, M D Jabali, P Johnson

J Biol Chem. 2001 Aug 3;276(31):28767-73.

PMID: 11369760

Abstract:

CD44 is a cell adhesion molecule implicated in leukocyte adhesion and migration, co-stimulation of T cells, and tumor metastasis. CD45 is a leukocyte-specific protein tyrosine phosphatase that dephosphorylates the Src family kinases, Lck and Fyn, in T cells. Positive regulation of Lck by CD45 is required for its effective participation in T cell receptor signaling events. Here, immobilized CD44 antibody induced a distinctive cell spreading in CD45(-), but not CD45(+), T cells, and this correlated with the induction of tyrosine-phosphorylated proteins. Two focal adhesion family kinases, Pyk2 and, to a lesser extent, FAK were inducibly phosphorylated, as was a potential substrate, Cas. CD44-mediated cell spreading and induced tyrosine phosphorylation were prevented by the Src family kinase inhibitor, PP2. Furthermore, 2-fold more Lck associated with CD44 in the low density sucrose fraction from CD45(-) T cells compared with CD45(+) T cells, suggesting that CD45 may regulate the association of Lck with CD44 in this fraction. Therefore, in CD45(-) T cells, CD44 signaling is mediated by Src family kinases, and this leads to Pyk2 phosphorylation, cytoskeletal changes, and cell spreading. This implicates CD45 in the negative regulation of Src family kinase-mediated CD44 signaling leading to T cell spreading.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP213743318-B	Lck Inhibitor - CAS 213743-31-8		213743-31-8	Price

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