Csk-binding protein can regulate Lyn signals controlling cell morphology.
The Src family kinase Lyn is involved in differentiation signals emanating from activated erythropoietin (Epo) receptors, it interacts with COOH-terminal Src kinase-binding protein (Cbp), an adaptor protein that recruits negative regulators COOH-terminal Src kinase (Csk) and suppressor of cytokine signaling-1 (SOCS1). Lyn phosphorylates Cbp on several tyrosine residues, including Tyr314, which recruits Csk/SOCS1, as well as Tyr381 and Tyr409 that bind Lyns own SH2 domain. We show that Cbp alters not only the ability of erythroid cells to differentiate but also their colony morphology. Consequently, we detailed the ability of Cbp to interact with and influence Lyns ability to initiate changes in cellular architecture, which affect cell-cell and cell-substratum interactions. Over-expression of active Lyn promotes filopodia formation while inactive Lyn promotes lamellipodia formation. Conversely, Cbp over-expression, which inhibits Lyn activity, promotes lamellipodia formation, while Cbp mutants preventing its interaction/signaling consequently allow Lyn to promote filopodia formation. Thus, the Lyn-Cbp pathway and subsequent regulation of Lyn signaling and cell morphology involves a dynamic and complex series of interactions.
Ingley
Evan
E
Cell Signalling Group, Laboratory for Cancer Medicine, Western Australian Institute for Medical Research and Centre for Medical Research, The University of Western Australia, Perth, Australia. eingley@waimr.uwa.edu.au
D000818:Animals; D019556:COS Cells; D048430:Cell Shape / Q000502:physiology; D002522:Chlorocebus aethiops; D015536:Down-Regulation; D041905:Erythroid Cells / Q000166:cytology / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D053614:Janus Kinase 2 / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism*
D008565:Membrane Proteins; C498709:Pag1 protein, mouse; D010750:Phosphoproteins; C491590:Socs1 protein, mouse; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D053614:Janus Kinase 2; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases