Structure and function of Cas-L, a 105-kD Crk-associated substrate-related protein that is involved in beta 1 integrin-mediated signaling in lymphocytes.
Integrin/ligand binding evokes tyrosine phosphorylation of various proteins. We reported previously that a 105 kD protein (pp105) was tyrosine phosphorylated by the engagement of beta 1 integrins in T lymphocytes. We show here that pp105 is a novel p130Cas (Crk-associated substrate)-related protein. Deduced amino acid sequence revealed that pp105 contains conserved motifs with p130Cas, and both pp105 and p130Cas bind to focal adhesion kinase (pp125FAK) and Crk. However, pp105 has a clearly distinct structure from p130Cas, and pp105 is preferentially expressed in lymphocytes, whereas p130Cas is expressed in adherent cells. With these findings, we designate pp105 as Cas-L, lymphocyte-type Cas. Furthermore, we demonstrate that integrin/ligand binding results in the recruitment of Crk, Nck, and SHPTP2 to pp105. These findings further define the roles of pp105/Cas-L and pp125FAK in the integrin-mediated signaling pathways.
Minegishi
M
M
Dana-Farber Cancer Institute, Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA.
Tachibana
K
K
Sato
T
T
Iwata
S
S
Nojima
Y
Y
Morimoto
C
C
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D019012:Integrin beta1 / Q000378:metabolism*; D008214:Lymphocytes / Q000502:physiology*; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011485:Protein Binding; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism*; D050721:Proto-Oncogene Proteins c-cbl; D050737:Proto-Oncogene Proteins c-crk; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction; D044767:Ubiquitin-Protein Ligases
D048868:Adaptor Proteins, Signal Transducing; D015815:Cell Adhesion Molecules; C493872:Crk protein, rat; D018076:DNA, Complementary; D019012:Integrin beta1; C099942:NEDD9 protein, human; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; D050737:Proto-Oncogene Proteins c-crk; D012333:RNA, Messenger; D011994:Recombinant Proteins; D050721:Proto-Oncogene Proteins c-cbl; D044767:Ubiquitin-Protein Ligases; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496052:Ptk2 protein, rat; C067419:CBL protein, human