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CBL — INS
Pathways - manually collected, often from reviews:
-
NCI Pathway Database Insulin Pathway:
CBL (CBL)
→
Insulin Receptor/Insulin/IRS1 complex (INSR-INS-IRS1)
(modification, collaborate)
Baumann et al., Nature 2000, Liu et al., Mol Cell Biol 2002, Hu et al., Mol Cell 2003, Ribon et al., Mol Cell Biol 1998
Evidence: mutant phenotype, assay, physical interaction
Text-mined interactions from Literome
Baumann et al., J Biol Chem 2000
:
c-Cbl associating protein (CAP) is a multifunctional signaling protein that interacts with c-Cbl, facilitating the tyrosine phosphorylation of
c-Cbl in
response to
insulin ... In 3T3-L1 adipocytes and diabetic rodents, CAP gene expression is stimulated by activators of peroxisome proliferator activator receptor gamma ( PPARgamma ), such as thiazolidinediones ( TZDs ), resulting in increased
insulin stimulated
c-Cbl phosphorylation
Baumann et al., J Biol Chem 2001
:
The
insulin stimulated translocation of
phospho-c-Cbl to lipid rafts, via its association with CAP, comprises a second pathway regulating GLUT4 translocation
Chiang et al., Nature 2001
:
We previously described a pathway involving the
insulin stimulated tyrosine phosphorylation of
Cbl , which is recruited to the insulin receptor by the adapter protein CAP
Liu et al., Mol Cell Biol 2002
:
Overexpression of the APS/Y ( 618 ) F mutant in 3T3-L1 adipocytes blocked the
insulin stimulated tyrosine phosphorylation of endogenous
Cbl and binding to Crk
Salt et al., J Biol Chem 2003
:
Furthermore, high glucose down-regulated the expression of CAP and Cbl, and
insulin stimulated
Cbl phosphorylation, components of an insulin signaling cascade previously characterized in adipocytes
JeBailey et al., Mol Endocrinol 2004
:
We found CAP expression and
insulin mediated
Cbl phosphorylation in differentiated myotubes but not in myoblasts
Shen et al., J Biol Chem 2004
(Body Weight...) :
In contrast, rosiglitazone increases the levels of CAP expression and
insulin stimulated
c-Cbl phosphorylation without affecting the IRS-1/Akt pathway
Ahn et al., J Biol Chem 2004
:
In cells co-expressing insulin receptor and CAP, without APS, no association of the insulin receptor and CAP could be detected and no
insulin stimulated phosphorylation of
Cbl was observed ...
Insulin stimulated
Cbl phosphorylation was reconstituted when APS was co-expressed with insulin receptor, with or without CAP ... In 3T3-L1 adipocytes, small interfering RNA mediated knockdown of the mouse APS gene abolished the
insulin stimulated phosphorylation of
c-Cbl ... Taken together, these results indicate that APS plays a central role in recruiting both CAP and c-Cbl to the insulin receptor after insulin stimulation and is necessary and sufficient for the
insulin stimulated phosphorylation of
c-Cbl , whereas SH2-Balpha may provide an alternative pathway for the recruitment of CAP
Standaert et al., Biochemistry 2004
:
Interestingly, these mutants inhibited
insulin induced increases in ( a ) binding of
Cbl to both Crk and the p85 subunit of PI 3-kinase, ( b ) activation of Cbl dependent PI 3-kinase, ( c ) activation and translocation of aPKC to the plasma membrane, ( d ) translocation of Glut4 to the plasma membrane, ( e ) and glucose transport
Miura et al., Biochemistry 2004
:
Knockout of IRS-1 or IRS-2 also inhibited
insulin induced increases in
Cbl binding to the p85 subunit of PI3K, which, along with IRS-1/2, may be required for activation of PI3K, aPKC, and glucose transport during insulin action in 3T3/L1 adipocytes
Mori et al., Mol Cell Endocrinol 2005
:
In spite of these differences, both FL-Grb10 and the BPS-SH2 fragment inhibited
insulin stimulated phosphorylation of IRS1, IRS2, Akt/PKB, Shc, ERK1/2, APS, and
c-Cbl to a similar extent
Sebastian et al., Am J Physiol Endocrinol Metab 2005
:
These results demonstrate that the impairment in insulin stimulated glucose transport observed in adipocytes after chronic ethanol feeding to rats is associated with a disruption of
insulin mediated
Cbl/TC10 signaling and actin polymerization
Gupte et al., Biochem Biophys Res Commun 2006
(Diabetes Mellitus...) :
In leptin-/- obese mice Cbl expression in heart and adipose tissue was maintained, although
insulin mediated
Cbl phosphorylation and subsequent TC10 activation were significantly reduced
Swaminathan et al., J Cell Physiol 2006
(Cell Transformation, Neoplastic) :
In addition, it addresses the functional requirements for E3 Ubiquitin ligase activity of Cbl and negative regulation of
Cbl mediated downregulation of PTKs, ( b ) Adaptor functions : This section discusses the mechanisms of adaptor functions of Cbl in mitogen activated protein kinase ( MAPK ) activation,
insulin signaling, regulation of Ras related protein 1 (Rap1), PI-3 ' kinase signaling, and regulation of Rho-family GTPases and cytoskeleton ; Biological functions : This section gives an account of the diverse biological functions of Cbl and includes the role of Cbl in transformation, T-cell signaling and thymus development, B-cell signaling, mast-cell degranulation, macrophage functions, bone development, neurite growth, platelet activation, muscle degeneration, and bacterial invasion ; Conclusions and perspectives
Saito et al., Metabolism 2008
:
In contrast, CAP protein concentration and
insulin stimulated plasma membrane
c-Cbl tyrosine phosphorylation were reduced by high-fat feeding ; but exercise training reversed these impairments
Wada et al., Am J Physiol Endocrinol Metab 2010
(Insulin Resistance) :
Interestingly,
insulin induced tyrosine phosphorylation of
Cbl and activation of TC10 were inhibited by progesterone at 10 ( -5 ) M
Mastick et al., J Biol Chem 1997
:
In 3T3-L1 adipocytes,
Cbl binds to Fyn in an
insulin dependent manner, and Cbl phosphorylation is adipocyte-specific
Chen et al., J Biol Chem 1997
:
In contrast,
insulin had no effect on CADTK but
stimulated the tyrosine phosphorylation of
Cbl and the tyrosine dephosphorylation of pp125(FAK) and p130 ( cas )
Ribon et al., Mol Cell Biol 1998
:
These results suggest a
role for tyrosine phosphorylated
c-Cbl in 3T3-L1 adipocyte activation by
insulin
Ribon et al., Proc Natl Acad Sci U S A 1998
(Insulin Resistance) :
c-Cbl associated protein ( CAP ) is a signaling protein that interacts with both c-Cbl and the insulin receptor that may be involved in the specific
insulin stimulated tyrosine phosphorylation of
c-Cbl ... This increased expression of CAP was accompanied by a potentiation of
insulin stimulated
c-Cbl tyrosine phosphorylation