Regulation of SR-BI-mediated selective lipid uptake in Chinese hamster ovary-derived cells by protein kinase signaling pathways

Scavenger receptor, class B, type I (SR-BI) mediates binding and internalization of a variety of lipoprotein and nonlipoprotein ligands, including HDL. Studies in genetically engineered mice revealed that SR-BI plays an important role in HDL reverse cholesterol transport and protection against atherosclerosis. Understanding how SR-BI's function is regulated may reveal new approaches to therapeutic intervention in atherosclerosis and heart disease. We utilized a model cell system to explore pathways involved in SR-BI-mediated lipid uptake from and signaling in response to distinct lipoprotein ligands: the physiological ligand, HDL, and a model ligand, acetyl LDL (AcLDL). In Chinese hamster ovary-derived cells, murine SR-BI (mSR-BI) mediates lipid uptake via distinct pathways that are dependent on the lipoprotein ligand. Furthermore, HDL and AcLDL activate distinct signaling pathways. Finally, mSR-BI-mediated selective lipid uptake versus endocytic uptake are differentially regulated by protein kinase signaling pathways. The protein kinase C (PKC) activator PMA and the phosphatidyl inositol 3-kinase inhibitor wortmannin increase the degree of mSR-BI-mediated selective lipid uptake, whereas a PKC inhibitor has the opposite effect. These data demonstrate that SR-BI's selective lipid uptake activity can be acutely regulated by intracellular signaling cascades, some of which can originate from HDL binding to murine SR-BI itself. Scavenger receptor, class B, type I (SR-BI) mediates binding and internalization of a variety of lipoprotein and nonlipoprotein ligands, including HDL. Studies in genetically engineered mice revealed that SR-BI plays an important role in HDL reverse cholesterol transport and protection against atherosclerosis. Understanding how SR-BI's function is regulated may reveal new approaches to therapeutic intervention in atherosclerosis and heart disease. We utilized a model cell system to explore pathways involved in SR-BI-mediated lipid uptake from and signaling in response to distinct lipoprotein ligands: the physiological ligand, HDL, and a model ligand, acetyl LDL (AcLDL). In Chinese hamster ovary-derived cells, murine SR-BI (mSR-BI) mediates lipid uptake via distinct pathways that are dependent on the lipoprotein ligand. Furthermore, HDL and AcLDL activate distinct signaling pathways. Finally, mSR-BI-mediated selective lipid uptake versus endocytic uptake are differentially regulated by protein kinase signaling pathways. The protein kinase C (PKC) activator PMA and the phosphatidyl inositol 3-kinase inhibitor wortmannin increase the degree of mSR-BI-mediated selective lipid uptake, whereas a PKC inhibitor has the opposite effect. These data demonstrate that SR-BI's selective lipid uptake activity can be acutely regulated by intracellular signaling cascades, some of which can originate from HDL binding to murine SR-BI itself. HDL plays an important role in protection against atherosclerosis, in part by mediating reverse cholesterol transport from macrophage foam cells in atherosclerotic plaque to the liver (1Lewis G.F. Rader D.J. New insights into the regulation of HDL metabolism and reverse cholesterol transport. Circ. Res. 2005; 96: 1221-1232Google Scholar). Elimination of scavenger receptor, class B, type I (SR-BI) expression in knock-out mice reduces hepatic HDL cholesterol clearance and biliary cholesterol secretion, and increases plasma levels of cholesterol associated with abnormally large, apolipoprotein E (apoE)-enriched HDL-like particles (as reviewed in Ref. 2Trigatti B. Kaur S.C. Role of the scavenger receptor class B type I in lipoprotein metabolism and atherosclerosis: insights from genetically altered mice. In Biochemistry of Atherosclerosis. Springer, New York2006: 53-69Google Scholar). Thus, in mice, SR-BI plays an important role, both in hepatic HDL-cholesterol clearance, and in driving reverse cholesterol transport. Inactivation of SR-BI expression renders mice more susceptible to atherosclerosis induced by high-fat, high-cholesterol diets or disruption of either apoE or LDL receptor expression (as reviewed in Ref. 2Trigatti B. Kaur S.C. Role of the scavenger receptor class B type I in lipoprotein metabolism and atherosclerosis: insights from genetically altered mice. In Biochemistry of Atherosclerosis. Springer, New York2006: 53-69Google Scholar). Mice deficient in both SR-BI and apoE develop severe occlusive coronary artery atherosclerosis and myocardial infarction and exhibit cardiac functional and conductance abnormalities prior to early death by 8 weeks of age (3Braun A. Trigatti B.L. Post M.J. Sato K. Simons M. Edelberg J.M. Rosenberg R.D. Schrenzel M. Krieger M. Loss of SR-BI expression leads to the early onset of occlusive atherosclerotic coronary artery disease, spontaneous myocardial infarctions, severe cardiac dysfunction, and premature death in apolipoprotein E-deficient mice. Circ. Res. 2002; 90: 270-276Google Scholar). Hepatic SR-BI overexpression increases clearance of plasma lipoprotein cholesterol and biliary cholesterol secretion and decreases atherosclerosis (although decreased HDL cholesterol levels at high levels of overexpression may diminish atheroprotection) (as reviewed in Ref. 2Trigatti B. Kaur S.C. Role of the scavenger receptor class B type I in lipoprotein metabolism and atherosclerosis: insights from genetically altered mice. In Biochemistry of Atherosclerosis. Springer, New York2006: 53-69Google Scholar). Elimination of SR-BI in bone marrow-derived cells, including macrophages, also results in increased atherosclerosis but without altering plasma lipoprotein cholesterol levels (4Covey S.D. Krieger M. Wang W. Penman M. Trigatti B.L. Scavenger receptor class B type I-mediated protection against atherosclerosis in LDL receptor-negative mice involves its expression in bone marrow-derived cells. Arterioscler. Thromb. Vasc. Biol. 2003; 23: 1589-1594Google Scholar, 5Zhang W. Yancey P.G. Su Y.R. Babaev V.R. Zhang Y. Fazio S. Linton M.F. Inactivation of macrophage scavenger receptor class B type I promotes atherosclerotic lesion development in apolipoprotein E-deficient mice. Circulation. 2003; 108: 2258-2263Google Scholar, 6Van Eck M. Bos I.S. Hildebrand R.B. Van Rij B.T. Van Berkel T.J. Dual role for scavenger receptor class B, type I on bone marrow-derived cells in atherosclerotic lesion development. Am. Scholar). Thus, both hepatic and macrophage SR-BI against atherosclerosis, and reverse cholesterol transport may be of pathways SR-BI is a receptor that can to a variety of ligands, including and and HDL, and HDL of (as reviewed in Ref. 2Trigatti B. Kaur S.C. Role of the scavenger receptor class B type I in lipoprotein metabolism and atherosclerosis: insights from genetically altered mice. In Biochemistry of Atherosclerosis. Springer, New York2006: 53-69Google Scholar). that of SR-BI are involved in its binding to distinct K. Krieger M. Scavenger receptor class B, type I-mediated to high and is dependent on lipoprotein binding to the Biol. Scholar, Krieger M. of the high lipoprotein and lipoprotein binding of murine scavenger receptor class B type I (mSR-BI) activity Biol. Scholar, M. Y. of lipid transport by in the of scavenger receptor class B, type Biol. 2003; Scholar). SR-BI mediates the of cells and with the of uptake versus by the lipid (as reviewed in Ref. P.G. M. of pathways of cholesterol Arterioscler. Thromb. Vasc. Biol. 2003; 23: Scholar). binding and lipid to be of and can SR-BI-mediated lipid without lipoprotein binding T.J. Penman M. Krieger M. of of the selective of by the HDL receptor 2002; Scholar). SR-BI is and to lipid in a variety of cell (as reviewed in Ref. 2Trigatti B. Kaur S.C. Role of the scavenger receptor class B type I in lipoprotein metabolism and atherosclerosis: insights from genetically altered mice. In Biochemistry of Atherosclerosis. Springer, New York2006: 53-69Google Scholar). internalization and to the cell In cells, cholesterol SR-BI from the to in a protein kinase C A. A. of the scavenger receptor class B type I in cells. Scholar). In and cells, of SR-BI to the cell from is induced by and dependent on the phosphatidyl inositol 3-kinase kinase signaling C and the of scavenger receptor class B, type I from intracellular to the plasma of Biol. 2005; Scholar, S. Post scavenger receptor class B type I and selective lipid uptake in Arterioscler. Thromb. Vasc. Biol. Scholar). scavenger receptor, class B, type I HDL lipid uptake to is B. Krieger M. scavenger receptor class B, type I into mediates high high lipoprotein binding and selective lipid Biol. 2002; and mSR-BI-mediated HDL lipid uptake in cells is by of T.J. M. Krieger M. is for the selective lipid uptake by murine 2005; Scholar, Hepatic SR-BI-mediated selective uptake with in the of Res. Scholar). SR-BI-mediated uptake by and to the to be dependent Hepatic SR-BI-mediated selective uptake with in the of Res. Scholar, A. transport for high lipoprotein and its associated in hepatic cells. Res. Scholar). Furthermore, the selective uptake of a of SR-BI with a and of a of SR-BI with an endocytic into its to be to increased B. lipoprotein uptake by scavenger receptor Biol. Scholar, S. A. Van lipoprotein by scavenger receptor is and a Biol. Scholar, B. S. of HDL in and Res. Scholar). the the and intracellular of a variety of ligands, including and cells is a for scavenger receptor class B type I and high lipoprotein binding and selective lipid Biol. 2005; Scholar, binding to and mediates of and protein Biol. 2005; Scholar, and internalization of by a of scavenger receptor Biol. 2003; Scholar, Y. A. K. A. Y. binding of class B scavenger receptor type a receptor of cells. Biol. 2002; Scholar, Y. A. Y. of protein in class B scavenger receptor type of cells. Res. Scholar). SR-BI-mediated cholesterol from cells also to be dependent on the internalization and of HDL S. A. W. M. SR-BI-mediated high lipoprotein leads to HDL cholesterol Biol. Scholar). HDL binding to SR-BI leads to of signaling pathways. These of protein M.F. signaling of the involves scavenger receptor type of Biol. 2003; Scholar, S. A. of and is by pathways in cells. of the kinase B M. A. lipoprotein binding to scavenger receptor, B, type I in a Biol. 2002; Scholar, HDL of a of HDL 2003; Scholar, I.S. M.J. is by and Biol. 2003; Scholar, K. A. M. A. lipoprotein receptor of cells. Res. and of protein kinase C (PKC) M.F. signaling of the involves scavenger receptor type of Biol. 2003; Scholar). HDL signaling SR-BI mediates the of in cells M. A. lipoprotein binding to scavenger receptor, B, type I in a Biol. 2002; Scholar, HDL of a of HDL 2003; Scholar, I.S. M.J. is by and Biol. 2003; Scholar, M. M. Su W. and in an 2003; Scholar, I.S. Y. S. lipoprotein binding to scavenger cell W. lipoprotein promotes cell and via scavenger type Circ. Res. and the of in cells K. A. M. A. lipoprotein receptor of cells. Res. Scholar, induced by scavenger receptor class B, type I and by and high Biol. 2005; Scholar). The signaling binding to its ligands, including HDL, but may of signaling cholesterol either into or of cells M. A. lipoprotein binding to scavenger receptor, B, type I in a Biol. 2002; Scholar, M. M. Su W. and in an 2003; Scholar, Sato K. K. A. M. lipoprotein cell and and its Arterioscler. Thromb. Vasc. Biol. 2003; 23: Scholar, I.S. M. and a of scavenger 2005; Scholar). signaling may the of SR-BI and may the binding of HDL of a of HDL 2003; Scholar, I.S. M.J. is by and Biol. 2003; including I.S. M. and a of scavenger 2005; Scholar, A. A. Krieger M. of SR-BI-mediated lipoprotein metabolism by the protein 2005; Scholar). SR-BI's for HDL lipid uptake, reverse cholesterol and protection against atherosclerosis in mice, is how its activity is regulated at the has that binding of phosphatidyl and cells leads to the of signaling kinase and which to Y. A. Y. of protein in class B scavenger receptor type of cells. Res. Scholar). In is the of signaling pathways by SR-BI's lipoprotein on SR-BI-mediated lipid demonstrate in a model cell system that SR-BI-mediated lipid uptake from distinct lipoprotein ligands, acetyl LDL and HDL, via distinct endocytic and pathways. We also demonstrate that the physiological ligand, HDL, but the model ligand, PKC activity in an whereas both and pathways. HDL also the of SR-BI on the cell in a that is dependent on or Finally, demonstrate that PKC and to an increased of uptake of to uptake of protein of increased selective lipid uptake activity of These data the that may be a at which SR-BI's activity is regulated and that PKC and may important in that from the and from by and and by from from and from from by The by from and B and from The protein and from from and wortmannin from and and from HDL and LDL from plasma by and with M.J. for the of the lipoprotein from Res. Scholar, and of the uptake of and by cells, and in Am. Scholar, S. A. S. Krieger M. of scavenger receptor SR-BI a high lipoprotein Scholar). and AcLDL by of either or LDL of lipoprotein and regulation of cholesterol metabolism in Scholar). HDL by of AcLDL from by by of lipoprotein and regulation of cholesterol metabolism in Scholar). against and by and at by of M. of Chinese hamster cell in the of Biol. Scholar). by on that mediates uptake and of cholesterol Scholar). The cell by Krieger of The of Chinese hamster cells, functional LDL receptor Krieger M. of lipoprotein in hamster cell with in the receptor Biol. cells SR-BI S. A. S. Krieger M. of scavenger receptor SR-BI a high lipoprotein and cells murine scavenger receptor class type I Penman M. S. M. Krieger M. and high and binding of murine type I and type macrophage scavenger Res. Scholar). in and cells in B that with and cells by cell with or for in B, from by in and in without for at with to The cells for the in the or of The cells on and of in and in of and for at with by of and cells by for at in a The cell with with and cells in and by at for and in the by (as for at with The in for for with and for with (as in the by for in of a and by the of of and for by and Trigatti B. A. S. Krieger M. a high lipoprotein receptor that mediates selective lipid uptake, is and and with plasma Biol. Scholar). in and for in B. with without by of cells at for in of by a at in either and or J.M. of intracellular and in Scholar). to or cells for at with of without or with A. and and or of either or with wortmannin but for with or without HDL, or to and for at with with from by in and by Trigatti B. S. S. Krieger M. The uptake of high lipoprotein via scavenger receptor class B type I binding but also lipid by its Biol. Scholar). cells to on and by cell in on by either a or a at and at or for and for The of the of cells a of the of uptake for In some a of either for both SR-BI and scavenger receptor, class type I or lipoprotein uptake the uptake the of and uptake the of We either or or In cells The of the uptake of to protein a of the degree of selective lipid at on a with a a and a for of The a and We the of on mSR-BI-mediated lipid uptake from lipoprotein We the physiological ligand, HDL, the model ligand, binding to involves distinct in the of the receptor K. Krieger M. Scavenger receptor class B, type I-mediated to high and is dependent on lipoprotein binding to the Biol. Scholar, Krieger M. of the high lipoprotein and lipoprotein binding of murine scavenger receptor class B type I (mSR-BI) activity Biol. Scholar). We cells, which a functional LDL receptor and high levels of scavenger to activity in the of pathways of lipoprotein either with or of intracellular which with by the of with B. and of and Biol. the of on the cell J.M. of intracellular and in Scholar, J.M. of intracellular and on function in and Scholar). and also the involved are A. and and Scholar). We also which The of of Biol. Scholar, A. of and which A. of Scholar, B. Role of in lipoprotein by cells. Scholar). T.J. M. Krieger M. is for the selective lipid uptake by murine 2005; decreased lipid uptake by a and In both cell of by scavenger receptor, class type I cells. These cells to of AcLDL M. Y. Penman M. Krieger M. of type I and type scavenger in Chinese hamster lipid and by and Scholar). also uptake by cells in with T.J. M. Krieger M. is for the selective lipid uptake by murine 2005; Scholar). In the uptake of which the and is in a that involves lipid but at the of mediates to transport by from the plasma of Biol. Scholar, Y. of the receptor from and by of Biol. 2002; Scholar). of cells with uptake whereas uptake of by of uptake by cells by by to or with uptake by cells of that by cells and with lipid uptake from uptake from either HDL or AcLDL by in cells B, or by in cells the of in both a and and a and and cells with and and and results for cells with These data that is for HDL lipid uptake by murine the data demonstrate that the receptor mediates lipid uptake from AcLDL via an endocytic that is dependent and of or disruption of or on murine scavenger receptor, class type I uptake or on uptake of B Chinese hamster cells endocytic receptor for or cells either of intracellular in or with of either or (as prior to with either or with a or for at cells in uptake of by the the of the with in the and of the uptake of by and for to of and cells. are of on without or with and with in by are and to We cell lipid uptake from either HDL or We cell a for the of on the cell for in the or the of either HDL or to the of SR-BI C A. A. of the scavenger receptor class B type I in cells. Scholar, S. A. M. M. of the uptake of HDL particles in cells via the scavenger receptor class B type Scholar, Wang lipoprotein uptake by scavenger receptor class B type results in selective of HDL cholesterol from protein and cholesterol Biol. to the internalization in The protein is for lipoprotein binding and internalization but for LDL receptor in Biol. Scholar). In the of and in the of a in cell in which cells at levels in cell of the cells with in the of cell decreased a in In HDL the in cell in Thus, HDL, but to on the cell by its These data are with the that mSR-BI-mediated lipid uptake from HDL and AcLDL via distinct pathways. mSR-BI-mediated uptake of from AcLDL has the of an endocytic whereas mSR-BI-mediated HDL lipid uptake to be of We that HDL and AcLDL with SR-BI may also signaling pathways. We the of and cells with either HDL or AcLDL HDL and AcLDL and of and of both and at and by in or protein We also the of HDL and AcLDL to PKC by the of a for with either HDL, or AcLDL in the or the of and The is a activator of a variety of PKC A. of kinase to signaling pathways. Biol. Scholar, PKC and of 2005; 23: and a for PKC is a PKC inhibitor A. of kinase to signaling pathways. Biol. Scholar). of cells with PMA induced with and by and HDL in a that also by In AcLDL the and with by an and that binding to for PKC in but of the protein kinase C (PKC) cells, in the to either HDL, or AcLDL at a of an or for at which on and by and for either or The data are of the and from a of the either the or the PKC signaling pathways are involved in of at the cell cells with and HDL either in the or the of the inhibitor for 3-kinase a or wortmannin to the cell of that the the PKC pathways cell in cells with in with its in and cells C and the of scavenger receptor class B, type I from intracellular to the plasma of Biol. 2005; Scholar, S. Post scavenger receptor class B type I and selective lipid uptake in Arterioscler. Thromb. Vasc. Biol. Scholar). HDL the in cell SR-BI and to its to the in cell SR-BI and and the of cell SR-BI Thus, of SR-BI on the cell to either PKC or signaling both by AcLDL that to of on the cell the of PKC and signaling pathways on the of selective lipid uptake by cells with either or and the uptake of both lipid and protein of HDL HDL that with and the levels of cell of lipid protein and the of cells with HDL, both and in a and in versus The of associated with cells at whereas the in the HDL of selective lipid of cells with PMA the cell of HDL lipid but cell of protein Thus, PMA increased the degree of selective lipid uptake cells HDL lipid but more HDL protein the degree of selective lipid uptake in both the and the of The of the PKC inhibitor to that of the which lipid uptake HDL binding to T.J. Penman M. Krieger M. of of the selective of by the HDL receptor 2002; Scholar). In wortmannin the of cell of HDL lipid but the cell of HDL in an increased degree of selective lipid uptake the mSR-BI-mediated selective lipid uptake to be by PKC and decreased by signaling in cells. We also the of and wortmannin on the uptake of lipid and protein from AcLDL in cells. for HDL, cells both and in a but versus by The of associated with cells with AcLDL 8 B, and whereas the in the AcLDL is with a more role in mSR-BI-mediated lipid uptake from AcLDL from HDL. of cells with cell of or from In of cells with wortmannin decreased cell of without cell of in an increase in the degree of selective lipid uptake of AcLDL lipid wortmannin to endocytic activity and to increase the of mSR-BI-mediated selective lipid uptake, of the lipoprotein ligand. We that mSR-BI-mediated lipid uptake from AcLDL and HDL via distinct pathways. mSR-BI-mediated lipid uptake from AcLDL has the of an endocytic which a of for the lipid versus the protein of the lipoprotein to and to to and by the These results are with that SR-BI mediates the of a variety of ligands, including phosphatidyl and cells is a for scavenger receptor class B type I and high lipoprotein binding and selective lipid Biol. 2005; Scholar, binding to and mediates of and protein Biol. 2005; Scholar, and internalization of by a of scavenger receptor Biol. 2003; Scholar, Y. A. Y. of protein in class B scavenger receptor type of cells. Res. Scholar, A. M. S. Scavenger receptor class B type I-mediated reverse cholesterol transport is by Biol. Scholar, of scavenger receptor class B type I by uptake and in cells. Biol. Scholar). In HDL the of on the cell in an and and SR-BI-mediated HDL lipid uptake data and the data of T.J. M. Krieger M. is for the selective lipid uptake by murine 2005; and Hepatic SR-BI-mediated selective uptake with in the of Res. The by which HDL and AcLDL lipid uptake pathways to be is SR-BI's S. A. S. of the scavenger receptor class B type and in cells and Res. Scholar, Scavenger receptor class B I (SR-BI) into and of in lipid Trigatti B. A. S. Krieger M. a high lipoprotein receptor that mediates selective lipid uptake, is and and with plasma Biol. endocytic versus or are by binding to distinct data that versus on the cell may be a at which SR-BI's selective uptake activity can be is with that that the selective uptake activity of a of which has a to be the of increased and that the of an endocytic into the of SR-BI to its increased and decreased selective lipid uptake activity S. A. Van lipoprotein by scavenger receptor is and a Biol. Scholar). results demonstrate that mSR-BI-mediated selective lipid uptake, in cells the receptor, is acutely regulated by protein kinase signaling pathways. PMA increases and decreases the degree of SR-BI-mediated selective lipid In the mSR-BI-mediated endocytic uptake of AcLDL that in cells, a and signaling SR-BI-mediated selective uptake and SR-BI-mediated PMA and are and is a inhibitor of both also including and the kinase A. of kinase to signaling pathways. Biol. Scholar, PKC and of 2005; 23: Scholar). The of the signaling SR-BI activity in cells, is The that HDL PKC activity (as by in an the of or more PKC and the that SR-BI's selective uptake activity may be to regulation by HDL. also to mSR-BI-mediated endocytic uptake and to selective lipid uptake, wortmannin the cell of lipoprotein particles protein the of selective lipid uptake for both HDL and from the in HDL selective lipid uptake in and cells C and the of scavenger receptor class B, type I from intracellular to the plasma of Biol. 2005; Scholar, S. Post scavenger receptor class B type I and selective lipid uptake in Arterioscler. Thromb. Vasc. Biol. Scholar). is is to in the cell type In demonstrate that in cells, wortmannin the of cell and that by HDL In in cells, wortmannin of SR-BI to the cell S. Post scavenger receptor class B type I and selective lipid uptake in Arterioscler. Thromb. Vasc. Biol. Scholar). the are with that wortmannin uptake of HDL particles S. Post scavenger receptor class B type I and selective lipid uptake in Arterioscler. Thromb. Vasc. Biol. and the transport of HDL particles from the to the of and of a model for hepatic lipoprotein transport. Scholar). are also with the that cells and phosphatidyl both of which are for SR-BI A. Krieger M. The class B scavenger SR-BI and are for Biol. Scholar, K. of a of scavenger receptor a receptor for high lipoprotein and Biol. to of and the and in cells Y. A. Y. of protein in class B scavenger receptor type of cells. Res. Scholar). of and activity in of cells and Y. A. Y. of protein in class B scavenger receptor type of cells. Res. Scholar). We that mSR-BI-mediated AcLDL lipid uptake is to and that cell of both AcLDL and HDL which binding and internalization of lipoprotein is by of cells with and Y. A. Y. of protein in class B scavenger receptor type of cells. Res. that cell of cells by and by the that AcLDL lipid uptake by in cells involves an endocytic is AcLDL lipid uptake by is also by of in a to SR-BI-mediated Y. A. Y. of protein in class B scavenger receptor type of cells. Res. Scholar). HDL, but PKC signaling in an in the cells. In both HDL and AcLDL the and pathways. is the that activate signaling pathways in the cells. the of by its is to signaling is of which may the of cholesterol either into or of signaling in the plasma I.S. M. and a of scavenger 2005; Scholar, M. from in cells. Biol. 2002; Scholar, Role of in Am. Scholar, with 2003; Scholar). the of from into cells M. A. lipoprotein binding to scavenger receptor, B, type I in a Biol. 2002; Scholar, M. M. Su W. and in an 2003; Scholar, Sato K. K. A. M. lipoprotein cell and and its Arterioscler. Thromb. Vasc. Biol. 2003; 23: Scholar, K. Sato K. A. A. M. lipoprotein of cells its Atherosclerosis. 2005; Scholar). SR-BI or more signaling that may to signaling In of an against the of SR-BI in cell HDL of a of HDL 2003; Scholar). Furthermore, a of SR-BI the which to HDL lipid uptake, to and of cells in K. A. M. A. lipoprotein receptor of cells. Res. Scholar). These that the of SR-BI may a role in at some signaling pathways. has that SR-BI's binding may in signaling in cells I.S. M. and a of scavenger 2005; Scholar). in signaling is In that SR-BI's selective uptake and endocytic can be regulated by the PKC and signaling at in cells. PKC and increase the of mSR-BI-mediated selective lipid uptake, whereas PKC and its the that SR-BI's selective uptake and endocytic may also be by protein kinase signaling in cell cells, macrophages, cells. These may important for SR-BI's in including reverse cholesterol transport and protection against atherosclerosis. The to SR-BI activity in both and cell in atherosclerotic by or of protein kinase signaling pathways be a therapeutic to the development of atherosclerosis and heart disease. Biol. that is involved in SR-BI-mediated HDL signaling in cells. The and for and for cell by in the by from the of the and of and the and of is a of the of New in and and is a and of New is a New with acetyl LDL apolipoprotein Chinese hamster B kinase protein kinase murine scavenger receptor class type I murine scavenger receptor class B type I phosphatidyl inositol 3-kinase protein kinase C scavenger receptor class type I scavenger receptor class B type I

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