Focal adhesion kinase-related fakB is regulated by the integrin LFA-1 and interacts with the SH3 domain of phospholipase C gamma 1.
Signal transduction through integrin molecules expressed on platelets and nonlymphoid cells involves activation of the intracellular focal adhesion kinase ppI25FAK (FAK) to phosphorylate substrate proteins on tyrosine residues. Similar mechanisms are also functional in T-lymphocytes through the beta 1-integrin VLA-4. A putative FAK-related phosphoprotein (fakB) was identified that is responsive to intracellular signals induced through ligation of antigen receptors on both T- and B-lymphocytes, and whose induced tyrosine phosphorylation is augmented by TCR costimulation through the adhesion/costimulatory receptors CD2 and CD4. In this report, fakB is shown to respond to extracellular signals through the beta 2-integrin LFA-1 in the absence of primary signals through the TCR. Protein-protein complex formation was observed involving an association between fakB, phospholipase C gamma 1 (PLC gamma 1), and the tyrosine phosphoprotein pp35-36. Evidence is provided here that fakB interacts with PLC gamma 1 through its SH3 domain. The association between fakB and PLC gamma 1 does not appear to require T-cell activation, whereas the induced tyrosine phosphorylation of the protein complex components occurs following engagement of LFA-1. These data indicate that the beta2-integrin LFA-1 expressed on T-lymphocytes stimulates a novel, FAK-related molecule that may function in the interplay between adhesion receptors and intracellular signaling enzymes responsible for downstream second messenger generation.
Kanner
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SB
Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, Washington 98121, USA.
D000595:Amino Acid Sequence; D015815:Cell Adhesion Molecules / Q000187:drug effects / Q000378:metabolism* / Q000494:pharmacology*; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D006801:Humans; D007527:Isoenzymes / Q000187:drug effects / Q000378:metabolism*; D015458:Leukemia, T-Cell; D016169:Lymphocyte Function-Associated Antigen-1 / Q000494:pharmacology*; D008969:Molecular Sequence Data; D051966:Phospholipase C gamma; D010750:Phosphoproteins / Q000032:analysis* / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000187:drug effects / Q000378:metabolism* / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D014407:Tumor Cells, Cultured; D010738:Type C Phospholipases / Q000187:drug effects / Q000378:metabolism*; D018909:src Homology Domains / Q000187:drug effects*
D015815:Cell Adhesion Molecules; D007527:Isoenzymes; D016169:Lymphocyte Function-Associated Antigen-1; D010750:Phosphoproteins; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human; D010738:Type C Phospholipases; D051966:Phospholipase C gamma